Abstracts - Cardiology Online · Ran Kornowski, Israel Smadar Kort, USA Santhosh K.G Koshy, USA...

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Abstracts

International Academy of Cardiology

Annual Scientific Sessions 2015

20th World Congress on Heart Disease

Vancouver, B.C., Canada, July 25–27, 2015

Guest Editor

Asher Kimchi, Los Angeles, Calif., USA

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INTERNATIONALACADEMY OFCARDIOLOGY

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Cardiology 2015:131(suppl 2) 1-403 International Academy of Cardiology Annual Scientific Sessions 2015 20th World Congress on Heart Disease

INTERNATIONAL ACADEMY OF CARDIOLOGY FOUNDER AND CONGRESS CHAIRMAN Asher Kimchi, USA SCIENTIFIC EXECUTIVE COMMITTEE John A. Elefteriades, USA (Chairman) Takashi Akasaka, Japan Matthew A. Allison, USA Martin Alpert, USA Ezra A. Amsterdam, USA Francisco Arabia, USA Wilbert S. Aronow, USA Subhash Banerjee, USA Elizabeth Barrett-Connor, USA Gregory Barsness, USA Lewis C. Becker, USA Daniel S. Berman, USA Deepak L. Bhatt, USA Robert W. W. Biederman, USA Yochai Birnbaum, USA Burns C. Blaxall, USA William Bommer, USA Jeffrey S. Borer, USA Neil E. Bowles, USA Sorin J. Brener, USA Michael E. Cain, USA Hari P. Chaliki, USA Yzhar Charuzi, USA Kanu Chatterjee, USA (deceased) Anne B. Curtis, USA Lawrence S.C. Czer, USA Sergio Dalla-Volta, Italy Alexander H.J. Danser, The Netherlands Thomas Deneke, Germany Naranjan S. Dhalla, Canada Uri Elkayam, USA Michael Farkouh, Canada Michael A. Fifer, USA Janos G. Filep, Canada Gordon L. Fung, USA Zorina Galis, USA Feng Gao, China Julius M. Gardin, USA A. Martin Gerdes, USA S. David Gertz, Israel Sidney Goldstein, USA Diana A. Gorog, UK Paul A. Heidenreich, USA Donald D. Heistad, USA Charles H. Hennekens, USA

Timothy D. Henry, USA Ramon C. Hermida, Spain Roland Hetzer, Germany Daniela Jezova, Slovakia Maryl R. Johnson, USA Bodh I Jugdutt, Canada Edo Kaluski, USA Ilan Kedan, USA Ali Khoynezhad, USA Lorrie Kirshenbaum, Canada Arthur L. Klatsky, USA Anne A. Knowlton, USA Stephen L. Kopecky, USA Adarsh Kumar, India Lih Kuo, USA Stephanie Lehoux, Canada Carlin S. Long, USA Gary Lopaschuk, Canada John J. Mahmarian, USA Kenneth Maiese, USA Tadeusz Malinski, USA Roberto Manfredini, Italy Ariane Marelli, Canada James D. Marsh, USA Jawahar L. Mehta, USA Luisa Mestroni, USA Dan M. Meyer, USA Leslie W. Miller, USA James K. Min, USA Freny Vaghaiwalla Mody, USA Samia Mora, USA Mohammad-Reza Movahed, USA Sherif F. Nagueh, USA Mohamad Navab, USA Kailash N. Pandey, USA Kaushik P. Patel, USA Patricia A. Pellikka, USA Christos Pitsavos, Greece Vittoria Pitzalis Zapler, USA Maria Prokudina, Russia Shahbudin H. Rahimtoola, USA Nalini M. Rajamannan, USA Hanumanth K. Reddy, USA Robert Roberts, Canada

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Robert S. Rosenson, USA Hani N. Sabbah, USA Masood Sadiq, Pakistan Tiziano M. Scarabelli, USA Saul Schaefer, USA Howard D. Sesso, USA Jamshid Shirani, USA Horst Sievert, Germany Pawan K. Singal, Canada Dinender Singla, USA Laurence Sperling, USA Francis G. Spinale, USA Jean-Francois Tanguay, Canada

Udho Thadani, USA Takanobu Tomaru, Japan Suresh C. Tyagi, USA Barry F. Uretsky, USA George W. Vetrovec, USA Nanette K. Wenger, USA Nathan D. Wong, USA

SCIENTIFIC ADVISORY BOARD

Mazen Abu-Fadel, USA Chris Adamopoulos, Greece Ali Ahmed, USA Elena Aikawa, USA Masanori Aikawa, USA Kannayiram Alagiakrishnan, USA Fernando Alfonso, Spain Aman Amanullah, USA Giuseppe Ambrosio, Italy Madhu B. Anand-Srivastava, Canada Dominick J. Angiolillo, USA Nestor J. Angomachalelis, Greece Charles Antzelevitch, USA Francisco Arabia, USA Juan M. Aranda, Jr., USA Eloisa Arbustini, Italy Pankaj Arora, USA Dan Atar, Norway Diana E. Ayala, Spain Luigi P. Badano, Italy Lina Badimon, Spain Maciej Banach, Poland Philip Barter, Australia Alexei G. Basnakian, USA Ronen Beeri, Israel Jonathan N. Bella, USA Gerald S. Berenson, USA Charles I. Berul, USA Luigi M. Biasucci, Italy Vera Bittner, USA Ron Blankstein, USA Peter C. Block, USA William E. Boden, USA Vicent Bodi, Spain Leonardo Bolognese, Italy Michiel L. Bots, The Netherlands Harisios Boudoulas, Greece Robert C. Bourge, USA

Thomas Braun, Germany Eugene Braunwald, USA John C. Burnett, Jr., USA Gianfranco Butera, Italy Samuel M. Butman, USA Hua Linda Cai, USA Duncan J. Campbell, Australia Ugur Canpolat, Turkey Noel M. Caplice, Ireland Hari P. Chaliki, USA Julie Y.H. Chan, Taiwan Farooq A. Chaudhry, USA Asim N. Cheema, Canada Changyi (Johnny) Chen, USA Jaw-Wen Chen, Taiwan Shih-Ann Chen, Taiwan Yi-Jen Chen, Taiwan Yingjie Chen, USA Xian Wu Cheng, Japan Yiu-Fai Cheung, China Anand Chockalingam, USA Kee-Joon Choi, South Korea Pierre Chouraqui, Israel Christina Chrysohoou, Greece Shorena Chumburidze, Georgia Quirino Ciampi, Italy Domenico Corrado, Italy Filippo Crea, Italy Luciano Daliento, Italy Michael Dandel, Germany Sandra T. Davidge, Canada Giuseppe De Luca, Italy Alan Y. Deng, Canada Milind Desai, USA Giovanni de Simone, Italy Christopher DeSouza, USA Yvan Devaux, Luxembourg André Diedrich, USA

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Luc Djousse, USA Dobromir Dobrev, Germany Stavros G. Drakos, USA Heinz Drexel, Germany Anique Ducharme, Canada Samuel Dudley, USA Daniel Duprez, USA Vladimír Džavík, Canada Thor Edvardsen, Norway Mohaned Egred, UK Andrew J. Einstein, USA Abdou Elhendy, USA Costanza Emaneuli, UK Georg Ertl, Germany Guo-Chang Fan, USA Mohamed Eid Fawzy, Egypt Nikolaos Frangogiannis, USA Stanley S. Franklin, USA Tohru Fukai, USA Joel A. Garcia, USA Peter Gaskin, USA Guido Germano, USA Bernard J. Gersh, USA J. Rod Gimbel, USA Uri Goldbourt, Israel Jonathan Golledge, Australia Michael H. Gollob, Canada Diana A. Gorog, UK Shmuel Gottlieb, Israel Peter J. Grant, USA Rajiv Gulati, USA Mariann Gyongyosi, Austria Abdul Hakeem, USA Ashraf Hamdan, Israel Jihong Han, China Stanley L. Hazen, USA Zuo-Xiang He, China Charles Henrikson, USA Michel Henry, Luxembourg Gerd Heusch, Germany Paul C. Ho, USA Brian D. Hoit, USA Myeong-Ki Hong, South Korea Masatsugu Hori, Japan Gang Hu, USA Heikki V. Huikuri, Finland Mansoor Husain, Canada Randolph Hutter, USA Borja Ibáñez, Spain Massimo Imazio, Italy Takafumi Ishida, Japan Allan S. Jaffe, USA Farouc Jaffer, USA Deepak Jain, Germany Jesper K. Jensen, Denmark Kai Jiao, USA

Xueting (Tina) Jin, USA Hanjoong Jo, USA Erik Jorgensen, Denmark J. Wouter Jukema, The Netherlands Alan H. Kadish, USA Andreas Kalogeropoulos, USA Duk-Hyun Kang, South Korea Samir Kapadia, USA Juan Carlos Kaski, UK Demosthenes G. Katritsis, Greece Osami Kawarada, Japan Amir Kazory, USA Matyas Keltai, Hungary Bijoy K. Khandheria, USA Yong-Jin Kim, South Korea Kwang Kon Koh, South Korea Igor E. Konstantinov, Australia Ran Kornowski, Israel Smadar Kort, USA Santhosh K.G Koshy, USA Thomas Krasemann, UK Rungroj Krittayaphong, Thailand Henry Krum, Australia Howard S. Kruth, USA Rakesh C. Kukreja, USA Sudhir Kurl, Finland Roger Laham, USA Dhanunjaya Lakkireddy, USA Roberto M. Lang, USA Alexandra Lansky, USA Gaetano A. Lanza, Italy Martin J. LaPage, USA Harold L. Lazar, USA Stephan E. Lehnart, Germany Robert A. Levine, USA T. Barry Levine, USA Qiangrong Liang, USA Philip R. Liebson, USA Shing-Jong Lin, Taiwan Wolfgang A. Linke, Germany Steven E. Lipshultz, USA Peter P. Liu, Canada Chaim Lotan, Israel Harry C. Lowe, Australia Alexandra Lucas, USA Xin-Liang Ma, USA Paolo Madeddu, UK Mohammad Madjid, USA Felix Mahfoud, Germany Bernhard Maisch, Germany Shaista Malik, USA Giuseppe Mancia, Italy Antoni Martinez Rubio, Spain Nilanjana Maulik, USA Pascal McKeown, Ireland Bruce M. McManus, Canada

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Issam Mikati, USA James C. Moon, UK Bassem Mora, USA Henning Morawietz, Germany Carlos A. Morillo, Canada Toshisuke Morita, Japan Alexander Morss, USA Thomas Muenzel, Germany Marjan Mujib, USA Barbara J. Mulder, The Netherlands Nandini Nair, USA Toshiaki Nakajima, Japan Khurram Nasir, USA Andrea Natale, USA Christopher Newton-Cheh, USA Arnold C. T. Ng, Australia Jens C. Nielsen, Denmark Yasushi Oginosawa, Japan Kenji Okumura, Japan Niels T. Olsen, Denmark Brian Olshansky, USA Torbjorn Omland, Norway Noriyuki Ouchi, Japan Ramdas G. Pai, USA Demosthenes B. Panagiotakos, Greece John T. Parissis, Greece Carlo Patrono, Italy Louis P. Perrault, Canada Jan J. Piek, The Netherlands Luc Pierard, Belgium Cristina Pislaru, USA Sorin Pislaru, USA Laurent Pison, The Netherlands Jorge Plutzky, USA Sunny S. Po, USA Don Poldermans, The Netherlands Kailash Prasad, Canada Karin Przyklenk, USA Vijay Puri, UK Lu Qi, USA Jeffrey J. Rade, USA Mohan K. Raizada, USA Satish R. Raj, Canada Shahzad G. Raja, UK Tienush Rassaf, Germany Judith G. Regensteiner, USA James A. Reiffel, USA Jun Ren, USA William C. Roberts, USA Joe L. Rod, USA Giuseppe M.C. Rosano, Italy Clive Rosendorff, USA Eric Rosenthal, UK Martin Huth H. Ruwald, Denmark Rajesh Sachdeva. USA Christoph Saely, Austria

Flora Sam, USA Habib Samady, USA Nilesh J. Samani, UK Prash Sanders, Australia Maria J. Sanz, Spain Maurice E. Sarano, USA Hiroshi Sato, Japan Naveed Sattar, UK Heinrich R. Schelbert, USA Ingolf Schimke, Germany Roland E. Schmieder, Germany Paul Schoenhagen, USA Karlheinz Seidl, Germany Roxy Senior, UK Rajat Sethi, USA Madhan Shanmugasundaram, USA Rakesh K. Sharma, USA Fayaz Shawl, USA Michael Shechter, Israel Win-Kuang Shen, USA Guo-Ping Shi, USA Avraham Shotan, Israel Rosa Sicari, Italy Mandeep S. Sidhu, USA Jean-Sébastien Silvestre, France Alain Simon, France Robert J. Siegel, USA Marc A. Silver, USA Christopher S. Snyder, USA Virend K. Somers, USA Jae-Kwan Song, South Korea Yiqing Song, USA Fabiola Sozzi, Italy V.S. Srinivas, USA Ashok K. Srivastava, Canada Deepak Srivastava, USA Komandoor Srivathsan, USA Paul Steendijk, The Netherlands Gustav Steinhoff, Germany Bodo-Eckehard Strauer, Germany Phyllis G. Supino, USA Jesper Hastrup Svendsen, Denmark Masafumi Takahashi, Japan Masahiko Takagi, Japan Akira Tamura, Japan László Tankó, Switzerland Paramjit Tappia, Canada Ahmed Tawakol, USA Andrew J. Taylor, Australia Mitsu Terashima, Japan Bernard Thibault, Canada Liza Thomas, Australia Dimitris Tousoulis, Greece Steven Tracy, USA Ronald J.A. Trent, Australia Masahiko Tsuchiya, Japan

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Balwant Tuana, Canada Dan Tzivoni, Israel Yasunori Ueda, Japan Mark K. Urman, USA Masuko Ushio-Fukai, USA Peter van der Meer, The Netherlands Orly Vardeny, USA Hector O. Ventura, USA Francesco Violi, Italy Johannes Waltenberger, Germany Da-Zhi Wang, USA Lu Wang, USA Qin Wang, USA Shi-Qiang Wang, China Xuejun Wang, USA Yibin Wang, USA S. Goya Wannamethee, UK Hiroshi Watanabe, Japan John Webb, Canada A. Teddy Weiss, Israel Cornelia M. Weyand, USA Harvey D. White, New Zealand R. Scott Wright, USA

Joseph C. Wu, USA Qingbo Xu, UK Sho-ichi Yamagishi, Japan Zhong-qun Yan, Sweden Clyde W. Yancy, USA Baofeng Yang, China Qinglin Yang, USA Masafumi Yano, Japan Jian (James) Ye, Canada Ertan Yetkin, Turkey Mitsuhiro Yokota, Japan Hiroshi Yoshida, Japan Cheuk-Man Yu, Hong Kong Xi-Yong Yu, China Maliha Zahid, USA Alberto Zanchetti, Italy Robert Zelis, USA Jianyi (Jay) Zhang, USA Youhua Zhang, USA Xi-Long Zheng, Canada Ming-Hui Zou, USA

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ABSTRACTS PRESENTED AT THE INTERNATIONAL ACADEMY OF CARDIOLOGY ANNUAL SCIENTIFIC SESSIONS 2015 20th WORLD CONGRESS ON HEART DISEASE Each abstract was graded by at least seven expert reviewers. Acceptance for presentation was based on the average score of all reviewers. A large number of excellent contributions were received and we thank both contributors and reviewers for their support, interest and effort. Asher Kimchi, MD Chairman SCIENTIFIC ABSTRACT REVIEW COMMITTEE Mazen Abu-Fadel, USA Chris Adamopoulos, Greece Takashi Akasaka, Japan Kannayiram Alagiakrishnan, USA Fernando Alfonso, Spain Matthew A. Allison, USA Madhu B. Anand-Srivastava, Canada Eloisa Arbustini, Italy Wilbert S. Aronow, USA Dan Atar, Norway Lina Badimon, Spain Gregory Barsness, USA Philip Barter, Australia Lewis C. Becker, USA Ronen Beeri, Israel Jonathan N. Bella, USA Charles Berul, USA Robert W. W. Biederman, USA Yochai Birnbaum, USA Vera Bittner, USA Peter C. Block, USA Jeffrey S. Borer, USA Sorin J. Brener, USA Gianfranco Butera, Italy Michael E. Cain, Israel Duncan J. Campbell, Australia Ugur Canpolat, Turkey Julie Y.H. Chan¸ Taiwan Yzhar Charuzi, USA Farooq A. Chaudhry, USA Asim N. Cheema, Canada Yingjie Chen, USA Xian Wu Cheng, Japan Anand Chockalingam, USA Kee-Joon Choi, South Korea Pierre Chouraqui, Israel Christina Chrysohoou, Greece Anne B. Curtis, USA Sergio Dalla Volta, Italy Alexander H.J. Danser, The Netherlands

Sandra T. Davidge, Canada Giovanni de Simone, Italy Yvan Devaux, Luxembourg Naranjan S. Dhalla, Canada André Diedrich, USA Samuel C. Dudley, USA Thor Edvardsen, Norway Mohaned Egred, UK Abdou Elhendy, USA Guo-Chang Fan, USA Michael Farkouh, Canada Mohamed E. Fawzy, Egypt Michael A. Fifer, USA Janos G. Filep, Canada Julius M. Gardin, USA Peter Gaskin, USA

A. Martin Gerdes, USA

S. David Gertz, Israel J. Rod Gimbel, USA Jonathan Golledge, Australia Mariann Gyongyosi, Austria Ashraf Hamdan, Israel Jihong Han, China Charles Henrikson, USA Michel Henry, Luxembourg Timothy D. Henry, USA Ramon C. Hermida, Spain Gerd Heusch, Germany Paul C. Ho, USA Brian D. Hoit, USA Myeong-Ki Hong, South Korea Masatsugu Hori, Japan Mansoor Husain, Canada Deepak Jain, Germany Jesper K. Jensen, Denmark Daniela Jezova, Slovakia Maryl R. Johnson, USA Xueting Jin, USA J.W. Jukema, The Netherlands Andreas P. Kalogeropoulos, USA

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Duk-Hyun Kang, South Korea Samir Kapadia, USA Amir Kazory, USA Ilan Kedan, USA Matyas Keltai, Hungary Raj Khandwalla, USA Ali Khoynezhad, USA Arthur L. Klatsky, USA Anne A. Knowlton, USA Kwang Kon Koh, South Korea Stephen L. Kopecky, USA Ran Kornowksi, Israel Rungroj Krittayaphong, Thailand Howard S. Kruth, USA Adarsh Kumar, India Lih Kuo, USA Sudhir Kurl, Finland Martin J. LaPage, USA Qiangrong Liang, USA Philip R. Liebson, USA Shing-Jong Lin, Taiwan Wolfgang A. Linke, Germany Carlin S. Long, USA Gary Lopaschuk, Canada Xin-Liang (Xin) Ma, USA Mohammad Madjid, USA Kenneth Maiese, USA Tadeusz Malinski, USA Roberto Manfredini, Italy James D. Marsh, USA Antoni Martinez-Rubio, Spain Nilanjana Maulik, USA Pascal McKeown, Ireland Luisa Mestroni, USA Jawahar L. Mehta, USA Leslie W. Miller, USA Henning Morawietz, Germany Carlos A. Morillo, Canada Toshisuke Morita, Japan Mohammad Reza Movahed, USA Barbara J. Mulder, The Netherlands Nandini Nair, USA Sherif S. Nagueh, USA Andrea Natale, USA Arnold C.T. Ng, Australia Jens C. Nielsen, Denmark Yasushi Oginosawa, Japan Kenji Okumura, Japan Kailash N. Pandey, USA Patricia A. Pellikka, USA Louis P. Perrault, Canada Vittoria Pitzalis Zapler, USA Sunny Po, USA Don Poldermans, The Netherlands Maria Prokudina, Russia Karin Przyklenk, USA

Shahbudin H. Rahimtoola, USA Shahzad G. Raja, UK Nalini M. Rajamannan, USA Tienush Rassaf, Germany James A. Reiffel, USA Jun Ren, USA Robert R. Rosenson, USA Martin H. Ruwald, Denmark Hani N. Sabbah, USA Nilesh J. Samani, UK Maria Jesus Sanz, Spain Tziano M. Scarabelli, USA Saul Schaefer, USA Ingolf Schimke, Germany Roland E. Schmieder, Germany

Paul Schoenhagen, USA Howard D. Sesso, USA Rakesh K. Sharma, USA Win-Kuang Shen, USA Guo-Ping Shi, USA Jamshid Shirani, USA Avraham Shotan, Israel Rosa Sicari, Italy Mandeep S. Sidhu, USA Horst Sievert, Germany Pawan K. Singal, Canada Marc Silver, USA Alain Simon, France Yiqing Song, USA Laurence Sperling, USA Francis G. Spinale, USA Ashok K. Srivastava, Canada Bodo-E. Strauer, Germany Jesper Hastrup Svendsen, Denmark Masafumi Takahashi, Japan Akira Tamura, Japan Mitsuyasu Terashima, Japan Takanobu Tomaru, Japan Steven Tracy, USA Masahiko Tsuchiya, Japan Suresh C. Tyagi, USA Yasunori Ueda, Japan Hector O. Ventura, USA A. Teddy Weiss, Israel Nanette K. Wenger, USA HarveyD. White, New Zealand Qingbo Xu, UK Qinglin Yang, USA Maliha Zahid, USA Alberto Zanchetti, Italy Robert Zelis, USA Youhua Zhang, USA Xi-Long Zheng, Canada

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CONTENTS SATURDAY, JULY 25, 2015 Abstract No. NOVEL CELLULAR MECHANISMS OF ATHEROSCLEROSIS 001 - 011

CARDIOVASCULAR IMAGING: FROM DIAGNOSIS TO PROGNOSIS 012 - 021 INTERVENTIONAL CARDIOLOGY / ANTITHROMBOTIC AND 022 - 028 ANTIPLATELET THERAPY IN PCI PEDIATRIC CARDIOLOGY AND CARDIAC SURGERY, 029 - 036 CONGENITAL HEART DISEASE SECONDARY PREVENTION, PROGNOSIS, RISK STRATIFICATION, 037 - 039 CARDIAC REHABILITATION LIPIDS, LIPOPROTEIN DISORDERS AND CAD 040 - 042 PREDICTORS AND MARKERS OF HEART FAILURE OUTCOME 043 - 044 PULMONARY CIRCULATION ASPECTS, PULMONARY HYPERTENSION 045 - 050 CARDIOVASCULAR ASPECTS IN RENAL DISEASE 051 - 052 CARDIOVASCULAR QUALITY IMPROVEMENT AND OUTCOME 053 - 057 COMPUTERS IN CARDIOLOGY 058 - 060 NEW INSIGHTS AND STRATEGIES FOR MYOCARDIAL REMODELING 061 - 067 AND HEART FAILURE

ARRHYTHMIA, ELECTROPHYSIOLOGY AND STROKE PREVENTION 068 - 076

ASSESSMENT AND MANAGEMENT OF CARDIOVASCULAR RISK / 077 - 085 MODIFICATION OF LIPOPROTEINS NEW DIRECTIONS IN CARDIOVASCULAR SURGERY: 086 - 092 HEART VALVE SURGERY / CORONARY REVASCULARIZATION / MECHANICAL CIRCULATORY SUPPORT / CARDIAC TRANSPLANTATION CELLULAR AND MOLECULAR MECHANISMS OF CARDIOPROTECTION, 093 - 098 CARDIAC REGENERATION AND REMODELLING

CHRONIC ISCHEMIC HEART DISEASE – MECHANISMS AND MANAGEMENT 099 - 105 ADVANCES IN HEART FAILURE, CARDIOMYOPATHIES AND 106 - 113 PULMONARY HYPERTENSION NEW DIAGNOSTIC METHODS AND IMAGING TECHNIQUES / 114 - 121 ECHOCARDIOGRAPHY

VASCULAR DISEASE (PERIPHERAL AND CAROTID), AORTIC DISEASES 122 - 123

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SATURDAY, JULY 25, 2015 Abstract No. BIOCHEMICAL MARKERS FOR RISK ASSESSMENT IN 124 - 126 CARDIOVASCULAR DISEASES PREVENTION OF CARDIOVASCULAR DISEASE: ASSESSMENT 127 - 130 AND MANAGEMENT OF CARDIOVASCULAR RISK HYPERTENSION: BASIC, CLINICAL AND EPIDEMIOLOGICAL 131 - 135 MECHANISMS OF ACUTE CORONARY SYNDROME: FROM BENCH TO BEDSIDE 136 - 141 ACUTE CORONARY SYNDROMES, INTERVENTIONAL THERAPIES 142 - 149 SUNDAY, JULY 26, 2015 Abstract No.

PATHOGENESIS, DIAGNOSIS AND TREATMENT OF AORTIC ANEURYSMS 150 - 157 AND PERIPHERAL ARTERY DISEASE CARDIOVASCULAR DISEASE AND CARDIOPROTECTION IN DIABETES 158 - 168 AND METABOLIC SYNDROME RISK STRATIFICATION AND SECONDARY PREVENTION OF CVD 169 - 176 VALVULAR / CONGENITAL HEART DISEASE, CARDIAC SURGERY 177 - 186

CARDIAC STRUCTURE AND FUNCTION IN FAILING AND NON-FAILING HEARTS 187 - 195

ADVANCES IN ARRHYTHMIA DETECTION, PREVENTION AND TREATMENT 196 - 203 NOVEL DIAGNOSTIC METHODS AND IMAGING TECHNIQUES 204 - 208 ACUTE MYOCARDIAL INFARCTION / REPERFUSION THERAPY 209 - 213 DIABETES MELLITUS, OBESITY, THE METABOLIC SYNDROME AND 214 - 219 ATHEROSCLEROSIS: BASIC AND CLINICAL

LEFT VENTRICULAR HYPERTROPHY / HYPERTROPHIC CARDIOMYOPATHY / 220 - 221 DIASTOLIC DYSFUNCTION CARDIOMYOPATHIES: PATHOGENESIS AND TREATMENT 222 - 229 NEW INSIGHTS INTO PATHOGENESIS AND MANAGEMENT OF HEART FAILURE 230 - 231

LIPIDS, STATINS AND CVD 232 - 240

CARDIOVASCULAR IMAGING MODALITIES FOR EVALUATION OF 241 - 247 CORONARY CIRCULATION, CARDIAC STRUCTURE AND FUNCTION CELLULAR AND MOLECULAR MECHANISMS OF CARDIOVASCULAR DISEASE, 248 - 255 BASIC RESEARCH

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SUNDAY, JULY 26, 2015 Abstract No. SYSTEMIC AND PULMONARY HYPERTENSION – RISK AND MANAGEMENT 256 - 265 ACUTE CORONARY SYNDROME: DETECTION, PREVENTION AND TREATMENT 266 - 273 MOLECULAR AND CELLULAR CARDIOLOGY / VASCULAR BIOLOGY, 274 - 284 BASIC RESEARCH

SYNCOPE AND SUDDEN DEATH: RISK ASSESSMENT AND MANAGEMENT 285 - 291 ARRHYTHMIAS: DIAGNOSIS AND TREATMENT – BASIC AND CLINICAL 292 - 299 PEDIATRIC CARDIOLOGY AND CARDIAC SURGERY / 300 - 302 CONGENITAL HEART DISEASE HEART VALVE DISEASE – CAUSES, SYMPTOMS, DIAGNOSIS AND TREATMENT 303 - 312 ADVANCES IN CARDIAC SURGERY: SURGICAL REVASCULARIZATION, 313 - 316 MECHANICAL CIRCULATORY SUPPORT / CARDIAC TRANSPLANTATION / CARDIAC MYXOMA MONDAY, JULY 27, 2015 CARDIOVASCULAR DISEASE PREVENTION AND RISK FACTORS 317 - 326 FROM MECHANISMS TO FUTURE DIRECTIONS IN THE TREATMENT AND 327 - 336 MANAGEMENT OF HEART FAILURE

VALVULAR HEART DISEASE MECHANISMS AND TREATMENT OPTIONS 337 - 342 CURRENT CONCEPTS AND FUTURE DIRECTIONS IN ISCHEMIC 343 - 352 HEART DISEASE AND ACUTE CORONARY SYNDROMES HEART FAILURE: NOVEL RISK FACTORS, BIOMARKERS, 353 - 361 NEW TREATMENT OPTIONS AND OUTCOME DIABETES, HYPERTENSION AND CARDIOVASCULAR DISEASE – 362 - 366 RISK AND MANAGEMENT MOLECULAR AND CELLULAR CARDIOLOGY, BASIC RESEARCH 367 - 372 VASCULAR BIOLOGY, BASIC AND TRANSLATIONAL RESEARCH 373 - 375 PROGRESS IN ECHOCARDIOGRAPHY 376 - 385 ATRIAL FIBRILLATION: DIAGNOSTIC ELECTROPHYSIOLOGY, 386 - 391 ABLATION AND STROKE PREVENTION MISCELLANEOUS 392

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ABSTRACTS

NOVEL CELLULAR MECHANISMS OF ATHEROSCLEROSIS

001

VASCULAR RESIDENT STEM CELLS IN ARTERIOSCLEROSIS

Q. Xu

King's College London, London, UK

Resident stem/progenitor cells in the adventitia and intima of the vessel wall have been implicated

in the pathogenesis of arteriosclerosis. Vascular lineage differentiation of stem cells can contribute

to both tissue repair and exacerbation of vascular diseases leading to restenosis in response to

angioplasty. The present presentation will focus on two aspects of progenitor cell plasticity in

arteriosclerosis. Firstly, we provide evidence that macrophages can induce functional endothelial

cell differentiation of the stem cells while simultaneously inhibiting their smooth muscle cell

differentiation. Mechanistically, both effects were mediated by macrophage-derived TNF via

TNF receptor 1 and canonical NF-kB activation. The lack of TNF in a knockout mouse model of

vein graft resulted in significant reduction of endothelial repair that led to thrombus formation.

Consistently, vessels from vein grafts carried out in knockout mice that received TNF+/+ bone

marrow cells showed a rescue of vascularization and prevention of thrombosis. Furthermore, we

found that treatment of the cells with sirolimus resulted in an induction of their migration and is

mediated specifically by CXCR4 activation. Ex vivo experiments using a decellularised vessel in

a bioreactor system confirmed the increment of vascular progenitor migration from the adventitial

side into the intima where they form neointima-like lesions in response to sirolimus. These findings

provide direct evidence of sirolimus-induced progenitor cell migration and differentiation into

smooth muscle cells via CXCR4 and EGFR/ERK/beta-catenin signal pathways, implicating a

novel mechanism of restenosis formation following sirolimus-eluting stent treatment. Finally, our

group recently established a new method to directly reprogramme mature cells into endothelial

lineage that was useful for promoting endothelial regeneration in vivo. Thus, vascular progenitor

cells can differentiate into either endothelial cells to repair the vessel or smooth muscle cells to

form neointimal lesions. A balance of stem/progenitor cell differentiation would be essential for

vascular hemostasis.

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002

EARLY DIAGNOSIS OF THE CARDIOVASCULAR SYSTEM - THE NANOMEDICAL

EVALUATION OF ENDOTHELIAL DYSFUNCTION T. Malinski, M.M. Rudek

Ohio University, Athens, Ohio, USA

Background: Endothelial dysfunction can be directly related to the dysfunction of the

cardiovascular system. The dysfunctional endothelium is characterized, among others, by the

deficiency of bioavailable nitric oxide (NO) and excess production of cytotoxic superoxide (O2-)

and peroxynitrite (ONOO-) – the main components of oxidative stress. The studies presented here

focus on the early assessment of endothelial dysfunction and its risk associated with the

development of cardiovascular diseases.

Methods & Results: We used a nanomedical approach (nanosensors with a diameter of 150-250

nm) to simultaneously measure the production of NO, O2-, and ONOO- in single HUVECs, of

different ethnicities (Caucasian, African American, Native American) and different gene variants

of endothelial nitric oxide synthase (eNOS). We introduced the parameter R, where R = [NO]/

[O2-] +[ONOO-], to measure the degree of endothelial dysfunction and the K as the rate of NO,

ONOO- and O2- production in nmol/s. R varied from about 3.5±0.4 to 1.8±0.3, indicating a

significant change in the function of eNOS variants. Dependent upon the eNOS gene variants and

ethnicity, the rate K, of NO production also varied from 180±25 nmol/s to 60±15 nmol/s. In a set

of separate experiments, [NO]/[O2-]+[ONOO-] balance/imbalance and the kinetics of NO, O2-

and ONOO production were also elucidated in the presence of environmental factors like elevated

glucose and/or elevated NaCl. Apparently, these environmental factors further increased

endothelial dysfunction, unfavorably shifting the [NO]/[O2-] + [ONOO-] balance. This effect was

additive to the effect of the gene variants.

Conclusion: The [NO]/ [O2-] +[ONOO-]ratio, as well as the rate of NO, ONOO- and O2-

generation, accurately reflects the functional state of the endothelium. This model can be used to

design a method for early diagnosis of cardiovascular diseases based on the analysis of a single

endothelial cell.

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003

NAVIGATING THE COMPLEXITIES OF APOPTOSIS AND AUTOPHAGY IN

CARDIOVASCULAR DISEASE: CAN WE CHART A CLEAR COURSE?

K. Maiese

University of Medicine & Dentistry of New Jersey, Newark, NJ, USA

The programmed cell death pathways of apoptosis and autophagy play a significant role in the

reparative and regenerative processes of the cardiovascular system. Apoptosis can control tissue

development and remodeling during the early stages of development. However, in mature cells

the induction of apoptosis can result in cell death. In contrast, autophagy, a process that can

promote cellular protection as well as cellular death involves the recycling of cytoplasmic

components and discards defective organelles for tissue remodeling. Multiple pathways can

ultimately influence apoptosis and autophagy in the cardiovascular system during injury, but a

number of new therapeutic strategies are focusing upon the role of extracellular matrix associated

proteins such as the CCN family of proteins. Of the CCN family members, Wnt1 inducible

signaling pathway protein 1 (WISP1) is increasingly being recognized as an exciting target for

tissue repair. WISP1 is intimately linked to pathways of regeneration that include

phosphatidylinositol-3-kinase (PI 3-K), protein kinase B (Akt), and the mechanistic target of

rapamycin (mTOR). Elucidating the potential of these novel reparative pathways and the ability

to govern apoptosis and autophagy offers new hope for the treatment of acute and chronic disorders

of the cardiovascular system.

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004

THE SECRET SUPREMACY OF SMALL BLOOD VESSELS, AN ENDURING PUZZLE

OF THE CARDIOVASCULAR SYSTEM: RESEARCH GAPS AND OPPORTUNITIES

Z.S. Galis

National Heart, Lung, and Blood Institute, Bethesda, MD, USA

Small blood vessels are a critical component of the vascular system and essential for the

maintenance and proper functioning of organs throughout the body. Their malfunction is a major

contributor to local and systemic diseases. In spite of being part of the same system, small blood

vessels have been studied traditionally within research and medical specialty silos aligning with

specific organs and the diseases affecting them. The enduring challenge stems from the limited

sharing and integration of the miscellaneous fundamental knowledge about diverse types of small

blood vessel across body systems necessary to gain a cohesive understanding of how they

individually and collectively function in health and disease. Emblematic for the “unity in diversity”

of small vessels is the endothelium, the inner cell layer covering all blood vessels yet selectively

mediating the local blood-tissue interactions. The endothelium can function as an only cellular

layer of tiniest blood vessels that mediate most blood-tissue exchanges. Their complexity rests on

anatomical and functional properties of specific endothelial cells, with extreme ability to respond

to local environmental cues and functional demands. At the body level, endothelium functions as

a complex mosaic layer, from creating completely tight barriers between blood and tissue to

allowing translocation of entire cells. Even more puzzling are the mechanisms controlling local

specificity of small blood vessel responses to systemic and long-range interactions, including

mechanical, electro-chemical, and blood-borne signals. Lack of appreciation for small blood vessel

complexity may be an important contributor to the bench-to the bedside gap in cardiovascular

research. Advancement will require a systems approach for integrating information, from

molecular to tissue to body level, informed by development of new sensitive biosensors and

imaging. Understanding and harnessing the phenotypic and functional heterogeneity of small

blood vessels may create new opportunities to specifically target tissues and organs for therapeutic

interventions.

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005

AGING, ESTROGEN, CELL SENESCENCE AND VASCULAR INFLAMMATION A.A. Knowlton1,2,3, H.V. Hwang2

1. Division of Cardiovascular Medicine, University of California, Davis, CA, USA

2. Pharmacology Department, University of California, Davis, CA, USA

3. Northern California VA, Sacramento, California, USA

Aging is characterized by the development of systemic inflammatory changes, organ dysfunction

and frailty. In females, loss of estrogen compounds these changes. Estrogen loss combined with

aging leads to increased oxidative stress, increased inflammation, dysfunctional EPCs leading to

impaired vascular repair, increased inflammation and increased monocyte adhesion. Cellular

senescence was thought to be benign, but it is now evident that senescent cells are pro-

inflammatory and may be associated with deleterious consequences in aging organisms that

accumulate senescent cells. Senescent endothelial cells secrete more pro-inflammatory factors

than non-senescent cells, and more disturbingly, may also incite pro-inflammatory secretion by

healthy non-senescent cells along with other negative functional changes. We hypothesized that

cell senescence, which increases with aging, is an important contributor to inflammation and

vascular dysfunction seen with aging, and that prevention or reduction in cell senescence can

mitigate the inflammatory changes associated with estrogen loss and aging. A corollary to this

hypothesis was that 17beta-estradiol (E2) will mitigate aging changes. To investigate this issue,

we co-cultured human microvascular smooth muscle cells (VSMC) with senescent (SEN) or early-

passage (EP) human endothelial cells (EC), separated by a permeable membrane to allow both

VSMC and EC to communicate with secreted factors. We found that the coculture of VSMC with

EC synergistically elevated secreted pro-inflammatory factors, IL-6, IL-8, and MCP-1. While both

SEN and EP cells promoted the cytokine and chemokine release, the amount released in SEN EC

– VSMC coculture was about 1.5- to 2- fold greater than with EP EC – VSMC. In addition, when

E2 was added to culture, the phospho-VASP/VASP ratio increased. These findings support the

potential role of senescent EC in aggravating hypertension and the persistent inflammatory

disorder that are common in older individuals, as well as the potential of E2 in aged individuals

to improve vascular function.

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006

CORONARY VASOMOTOR REGULATION BY CRP AND LOX-1 RECEPTORS L. Kuo, T.W. Hein

Texas A&M Health Science Center, Temple, TX, USA

Recent evidence suggests that C-reactive protein (CRP) is an independent cardiovascular risk

marker and also a mediator of inflammation and atherogenesis. Studies in cultured endothelium

implicate that lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) or Fc-gamma

receptor II (CD32) contributes to the pro-atherogenic effects of CRP. However, it is unclear

whether CRP exerts adverse action in the coronary microcirculation and the identity of the CRP

receptors linking to vasomotor function remains unknown. To address these issues, porcine

coronary arterioles (50-100 micrometer in diameter) were isolated for videomicroscopic analysis

of vasomotor activity, dihydroethidium fluorescence detection of superoxide,

immunohistochemical localization of receptors, immunoprecipitation of receptor/CRP interaction,

and protein blot. Intraluminal treatment of pressurized arterioles with a pathophysiological level

of CRP (7 µg/mL, 60 minutes) attenuated endothelium-dependent nitric oxide (NO)-mediated and

prostacyclin (PGI2)-mediated dilations to serotonin and arachidonic acid, respectively. The

adverse effect of CRP was prevented by superoxide scavenger Tempol and NADPH oxidase

inhibitor apocynin. LOX-1 and CD32 were both detected in the endothelium of arterioles.

Blockade of LOX-1 with either pharmacological antagonist -carrageenan or anti-LOX-1 antibody

prevented the detrimental effect of CRP on vasodilator function, whereas anti-CD32 antibody

treatment was ineffective. Denudation of endothelium and blockade of LOX-1 but not CD32

prevented CRP-induced elevation of superoxide in the vessel wall. CRP was co-

immunoprecipitated with LOX-1 and CD32 from CRP-treated arterioles. Similarly, blockade of

LOX-1 and CD32 both prevented CRP-induced arteriolar expression of plasminogen activator

inhibitor-1 (PAI-1), a thrombogenic protein. We conclude that CRP elicits endothelium-dependent

oxidative stress and compromises NO- and PGI2-mediated vasomotor function via LOX-1

activation. By contrast, both LOX-1 and CD32 mediate PAI-1 upregulation in arterioles by CRP.

Thus, activation of LOX-1 and CD32 may contribute to vasomotor dysfunction and pro-

atherogenic actions of CRP, respectively.

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007

REGULATION OF EARLY GROWTH RESPONSE PROTEIN-1 IN VASCULAR

SMOOTH MUSCLE CELLS

A.K. Srivastava Centre Hospitalier de l' Universite de Montreal, Montreal, QC, Canada

Hyperactivation of proliferative and growth promoting pathways underlies the progression of

vessel remodeling leading to vascular dysfunction. An upregulation of early growth response

protein 1 (Egr-1), a zinc finger transcription factor has been observed in several models of vascular

diseases. In an attempt to understand the mechanisms that contribute to the upregulation of Egr-1

in these models we have investigated the role of vasoactive peptides such as Endothelin-1 (ET-1),

Angiotensin II (Ang II) and growth factors such as insulin- like growth factor -1 (IGF-1) on the

expression of Egr-1 in vascular smooth muscle cells (VSMC) Here we show that ET-1, Ang II and

IGF-1 potently enhanced both protein and mRNA expression of Egr-1 in these cells.

Pharmacological blockade of ERK1/2, PI3K/PKB pathways by PD98059/Wortmannin/SC-66

respectively, significantly attenuated Egr-1 expression by these factors. DPI

(Diphenyleneiodonium), an inhibitor of NAD(P)H oxidase, blocked the activation of ERK1/2 and

PKB as well Egr-1 expression in response to these factors. In summary, these data demonstrate

that ROS-dependent activation of ERK1/2 and PI3K/PKB, the key growth promoting pathways in

VSMC, by vasoactive peptides and growth factors plays a critical role the upregulation of Egr-1

in vascular system. (Supported by CIHR).

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008

CARDIOVASCULAR EFFECTS OF CARFILZOMIB, A NEW PROTEASOME

INHIBITOR, ON CORONARY RESISTENCIES, VASCULAR TONE AND VASCULAR

REACTIVITY

T.M. Scarabelli

The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount

Sinai, New York, USA

Background: Carfilzomib (CFZ) is a new proteasome inhibitor used for the treatment of relapsed

and/or refractory Multiple Myeloma. Cardiac failure events (7.2%) and myocardial ischemia have

occurred following administration CFZ. Infusion reactions also include chest thightness and

angina of unknown mechanism.

Aim of study: To test the effects of CFZ (10-9 to 10-7 mol/L) on the isolated rabbit heart and aorta.

Methods and Results: CFZ administered in the perfusate to the isolated heart did not substantially

modify left ventricular pressure (LVP) and heart rate (HR), whereas coronary perfusion pressure

(CPP) was only slightly increased at the highest concentration used (from 65.2 +/- 4.1 to 78.6 +/-

8.3 mm Hg; p<0.05). Conversely, administration of CFZ by pulse injection caused a significant

increase in CPP at all concentrations used (all p<0.05) and a mild, though significant, rise in LVP

and HR at the highest concentration. Carfilzomib administered directly into the organ bath

significantly increased the basal tone of the isolated aortic strips (e.g. 0.58 +/- 0.04 at 10-7 mol/L)

with plateau of contraction reached after 10 minutes (all p<0.05). Such spasmogenic effect was

basically doubled following ablation of the endothelium. Pretreatment with CFZ for 60 minutes

significantly amplified the vasospastic action exerted by 3 different agents, i.e. KCl, noradrenaline

(NA) and angiotensin II (A), on aortic strips; and impaired vasodilation following administration

of nitroglycerin (NTG) and nifedipine (NFP) on the plateau of contraction induced by KCl, NA

and A (all p<0.05). Likewise, aortic strips pretreated with CFZ exhibited impaired relaxation, as

compared to untreated strips, following administration of acetylcholine (Ach), an endothelium-

dependent vasodilating agent, on the plateau of NA contraction (p<0.05).

Conclusions: CFZ increased CPP, resting vasoconstricting tone and the spasmogenic effect of

different agents. Preincubation with CFZ decreased the anti-spasmogenic activity of NTG and

NFP, as well as reduced by over 50% the vasodilating effect of Ach, suggesting that CFZ can

impair vasodilation via an endothelium dependent mechanism. Further studies are warranted to

establish its clinical safety in patients with known CAD and prior history of coronary spasm.

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009

ASPIRIN-INSENSITIVE THROMBOXANE GENERATION AS A MARKER OF

ENDOTHELIAL DYSFUNCTION

J.J. Rade

University of Massachusetts Medical School, Worcester, MA, USA

Thromboxane A2 (TXA2) is a signal-dependent prostanoid generated from the metabolism of

arachidonic acid by the cyclooxygenase (COX) and thromboxane synthase enzymes. In healthy

adults, TXA2 is almost exclusively produced in platelets where it mediates platelet activation and

vasoconstriction. Aspirin exerts its principle antiplatelet effect by suppressing TXA2 generation

by irreversibly inhibiting platelet COX-1. Data from several clinical studies reveal that patients

with cardiovascular disease and evidence of persistent TXA2 generation despite aspirin therapy

are at increased risk of adverse cardiac events. In a study of patients undergoing cardiac surgery,

we found that while aspirin was highly effective at suppressing platelet TXA2 generation, a

substantial number continued to generate TXA2 from apparent non-platelet sources. This aspirin-

insensitive TXA2 generation was found to be a novel risk factor for early graft thrombosis and

strongly associated with increased oxidative stress. In vitro studies subsequently confirmed that

endothelial cells are capable of generating TXA2 in response to a number of stimuli, including

oxidative stress. Isoprostanes, generated by non-enzymatic metabolism of arachidonic acid under

conditions of oxidative stress, appear able to act as mediators of endothelial TXA2 generation.

Studies by several laboratories, including our own, suggest that TXA2 is capable of altering

endothelial thromboresistance by modulating the expression of tissue factor and inflammatory

adhesion molecules. This may provide an explanation for the increased risk of thrombotic events

associated with aspirin-insensitive TXA2 generation observed in clinical studies. In contrast to

platelet TXA2 generation, aspirin is ineffective at inhibiting TXA2 generation in endothelial cells

given its short circulating half-life and the ability of nucleated cells to regenerate inhibited COX-

1. Potential strategies to suppress endothelial TXA2 generation include TXA2 synthase

inhibitors/receptor antagonists, antioxidants and/or polyunsaturated fatty acids.

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010

REGULATION OF MYOCARDIN ACTIVITY IN VASCULAR SMOOTH MUSCLE

X-L. Zheng

Department of Biochemistry & Molecular Biology, Libin Cardiovascular Institute of Alberta,

Cumming School of Medicine, University of Calgary, Canada

Many vascular diseases result from dedifferentiation of vascular smooth muscle cells (SMCs).

Myocardin (MYOCD) is a co-transcriptional activator of serum response factor (SRF) and

stimulates the expression of SM genes and inhibits the cell cycle. In addition to its roles in the

development, MYOCD is critically involved in the pathogenesis of proliferative vascular diseases.

The expression and activity of MYOCD are tightly regulated in SMCs. MYOCD, when

phosphorylated by GSK-3β, can be ubiquitinated by C-terminus of Hsc70-interacting protein

(CHIP), a cytosolic E3 ligase, resulting in proteasomal degradation and reduction of MYOCD

transcriptional activity. More recent studies from our laboratory have indicated that inhibition of

MYOCD degradation blocks MYOCD activity and tumor necrosis factor-alpha phenotype-

specifically regulates MYOCD activities in SMCs. In summary, the regulation of MYOCD activity

may play a critical role in the pathogenesis of vascular disease.

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011

ATHEROSCLEROSIS, CANCER AND WOUND HEALING; THE SYSTEMS BIOLOGY

CONNECTION A.R. Lucas1,2, S. Ambadapadi1,2, S. Morshed1,2, G. Munuswamy Ramanujam1,

D. Zheng1, R. Thoburn3, L. Liu4, E. Dai4, K. Lakshmyya5, G. McFadden2

1. Department Medicine, Division Cardiology, University of Florida, USA

2. Molecular Genetics and Microbiology, University of Florida, USA

3. Department Medicine, Division Rheumatology, University of Florida, USA

4. Brigham and Women Hospital, Harvard Medical School, USA

5. Department of Periodontology, College of Dentistry, University of Florida, USA

Serpins have critical regulatory roles in coagulation, inflammatory, and apoptosis, representing a

large percentage of circulating proteins. Genetic serpin mutations cause severe disorders such as

deficiency in alpha1 antitrypsin and neuroserpin or in sepsis with disseminated intravascular

coagulation. Modified serpin activity is used in treating clinical disorders, i.e. heparin decreases

clotting through activation of anti-thrombin (SERPINC1) and alpha anti-trypsin replacement

(SERPINA1) is given to patients with genetic deficiency and emphysema. Prior studies report the

use of serpin peptides for treatment in sepsis and HIV. Our research group is examining virus-

derived serpins as potential therapeutics. Prior work demonstrated significant reductions in

vascular disease with the Myxomaviral serpin, Serp-1, in models of arterial balloon angioplasty

and aortic, renal and cardiac transplants. Serp-1 treatment also improved mortality in lethal Mouse

gamma herpes virus (MHV68) infection where we detected marked reductions in pulmonary

hemorrhage and congestion Serp-1 has also been tested in a phase 2A clinical trial after coronary

stent implant for patients with unstable coronary syndromes (NSTEMI) with a demonstrated

significant reduction in markers for myocardial damage. Another Myxomavirus derived serpin,

Serp-2, that targets the infammasome and apoptotic pathways markedly reduced anti-

inflammatory activity in animal models of vascular surgery, ischemia reperfusion injury and

transplant, whereas CrmA from Cowpox was inactive. Related work using mammalian serpins

such as neuroserpin (SERPINI1) also demonstrated anti-inflammatory activity and reduced tumor

growth in animal models. In recent work we assessed the capacity of serpin reactive center loop

(RCL) peptides to expand serpin functions and reduce inflammatory responses detecting

reductions in plaque growth in an aortic transplant models and improved survival in lethal MHV68

infection model. In conclusion, viral serpins have evolved over many millions of years to form

highly efficient regulators of central inflammatory pathways, identifying shared pathogenic

pathways driving disease and new therapeutic horizons.

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24


CARDIOVASCULAR IMAGING: FROM DIAGNOSIS TO PROGNOSIS

012

DETERMINANTS OF CARDIAC FUNCTION IN PATIENTS WITH DILATED

CARDIOMYOPATHY

S.F. Nagueh

Methodist DeBakey Heart and Vascular Center, Houston, TX, USA

Interstitial fibrosis is common in patients with advanced heart failure, including those with dilated

cardiomyopathy (DCM). Echocardiography and right heart catheterization were utilized to assess

left ventricular (LV) function and cardiac tissue was obtained to study myocardial structure and

the gene and protein expression of several proteins that affect cellular function and fibrosis. LV

systolic and diastolic function were significantly related to the mRNA and protein levels of

SERCA 2a and PLB as well as mRNA levels of TTN N2B and N2BA. On the other hand, weak

to no associations were present between myocardial function and interstitial fibrosis and its

molecular determinants. LV systolic and diastolic functions in DCM are primarily associated with

myocardial force generation/relaxation elements.

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013

PREDICTING LONG-TERM RISK IN GENERALLY ASYMPTOMATIC PATIENTS:

CARDIAC TESTING IN A MULTIMODALITY IMAGING WORLD S. Chang1, F. Nabi1, J. Xu2, J. Mahmarian1

1. Houston Methodist DeBakey Heart and Vascular Center, Houston, TX, USA

2. Houston Methodist Research Institute, Houston, TX, USA

Although coronary artery calcium score (CACS), exercise treadmill test (ETT), and stress

myocardial perfusion tomography (SPECT) results predict patient outcome, there are no data

comparing their relative value in risk stratification. We performed a prospective, observational

study in 988 asymptomatic or low-risk symptomatic patients without prior coronary artery disease

to define relative value of these tests in predicting long-term (median follow-up 6.9 years) cardiac

events. Most patients (87%) were appropriate candidates for functional testing based on current

guidelines. The cardiac event rate was 11.2% (1.6%/ year). Multivariate risk predictors in all

patients and in the appropriate use cohort were abnormal SPECT (hazard ratio [HR]: 1.83 and

1.99), ETT ischemia (HR: 1.70 and 1.76), decreasing Duke treadmill score (HR: 1.07 for both),

and CACS severity (HR: 1.29 for both), respectively. CACS improved risk prediction in all

patients, in the appropriate use cohort and in those with low-risk ETT and SPECT results (all,

p<0.001). Area under the receiver operating characteristic curve increased when CACS (from 0.63

to 0.70; p=0.01) but not ETT variables (from 0.63 to 0.65) were added to Framingham risk score

(FRS). Net reclassification improvement significantly increased by adding CACS to FRS +

functional variables (p<0.0001). Thus, CACS significantly improved long-term risk stratification

beyond FRS, ETT, and SPECT results across all FRS groups, among those currently considered

appropriate candidates for functional testing and in those with low-risk functional test results. Our

findings support CACS as a first-line test over ETT or SPECT for assessing long-term risk in such

patients.

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014

CAC TESTING IN 2015: ROLE IN SHARED DECISION MAKING?

K. Nasir

Center for Wellness and Prevention Baptist Health South Florida, Miami Beach, FL, USA

In both the US and Europe, there have been significant declines in deaths due to cardiovascular

disease (CVD) over the last two decades. The impressive reduction in mortality is reassuring

evidence of the success of enhanced preventive efforts including lifestyle interventions and the

appropriate use of preventive medications such as statins. The recent ACC/AHA guidelines on risk

assessment and cholesterol treatment shifted the paradigm of statin eligibility in primary

prevention from a combination of risk assessment and corresponding LDL cholesterol targets to a

risk-based decision alone, shared between the provider and the patient. However with wide

broadening of the scope of individuals meeting criteria for statin has brought new challenges. With

current guidelines more than 12 million additional individuals in US and overall 1 billion

individuals worldwide will be candidates for statins with the cost of generic statin to be around 1

trillion dollars in 2020. Moreover emerging evidence suggest that approximately half of those

considered at high risk by current risk calculators are actually at lower risk of events resulting in

appropriate use of statin. Coronary artery calcium (CAC) as a surrogate for coronary

atherosclerotic burden has been consistently shown to identify those at higher risk and thus

appropriate candidates for statin. Moreover absence of CAC (power of zero) have been noted in

30-50% of those considered at high risk by traditional strategies among whom statins can be safely

avoided with a focus on lifestyle interventions. In 2015, CAC testing has the potential to

appropriately identify candidates who will, and will not, benefit from lifelong statin therapy and

facilitate shared decision making and resource allocation among the stakeholders.

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015

CURRENT STATUS OF INTRAVASCULAR IMAGING

S.K. Koshy

University of Tennessee Health Sciences Center, Memphis, Tennessee, USA and Regional One

Health, Memphis, Tennessee, USA

Currently available intravascular imaging techniques that are used in clinical practice, have major

limitations related to resolution and ease of imaging. There have been major innovations in the

field of imaging to improve on these limitations and to incorporate novel imaging techniques that

venture beyond the traditional delineation of anatomical intravascular structures. Intravascular

Ultrasound (IVUS) imaging and Optical Coherence Tomography (OCT) are now widely used in

clinical practice. However the frustrating impediment of lack of high grade resolution has been a

major handicap for clinicians. Advances in ultrasound and tomographic physics have made

possible major path breaking initiatives to improve axial, lateral and temporal resolutions. Ease of

imaging has improved with technological advancement in catheter designs and in techniques that

allow tomographic imaging without interrupting blood flow. Tissue imaging of subcellular

components and chemicals can be combined with traditional imaging to obtain additional valuable

information. Near infrared spectroscopy and time-resolved fluorescence spectroscopy are two

novel imaging techniques that have potential to be incorporated into the traditional imaging

techniques like IVUS, OCT, angioscopy, Computerized Tomographic angiography and Magnetic

Resonance Imaging. Hybrid techniques involving two or more imaging methods will improve the

applicability and utility of intravascular imaging in clinical practice.

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016

SAFETY AND EFFICACY OF DUAL MOTION ROTATIONAL CORONARY

ANGIOGRAPHY

J.A. Garcia

Orlando Health, Orlando, FL, USA

Background: Cardiac catheterization via standard angiography (SA) requires several angiograms

while rotational coronary angiography (RA) employs the use of automated gantry acquisitions

(LAO to RAO with a fixed cranial or caudal angulation) permitting complete visualization of the

entire coronary tree via two injections of the left (LCA) (cranial and caudal) and one of the right

coronary tree (RCA). XperSwing dual-axis rotational coronary angiography (DARCA) is a novel

acquisition method wherein the gantry automatically rotates both LAO/RAO and cranial/caudal in

one cine permitting complete visualization of a coronary tree with a single injection (Figure 1).

We sought to compare DARCA to SA with respect to time, contrast and radiation dose.

Methods: 15 patients underwent SA and DARCA for both coronary trees. Contrast, dose-area

product (DAP) and time (mean ±SD) were recorded for each and compared using a Student’s t-

test. For DARCA, blood pressure (BP), heart rate (HR), symptoms and ectopy were recorded for

each prolonged coronary injection.

Results: DARCA significantly reduced the amount of contrast used (28.9±4.2 vs.55.3±12ml;

p=0.0002), radiation dose (23.9±6.3 vs. 38.5±11.7 Gy/cm2: p=0.0003) and procedural time

(158.5±40.2 vs. 221.9±61.5 seconds; p=0.0028) when compared to SA. There were no significant

changes in BP, HR nor development of symptoms/ectopy during DARCA.

Conclusion: DARCA is a novel, safe and effective angiographic acquisition technique which

significantly reduces contrast, radiation exposure and procedural time when compared to SA.

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017

EMERGING NONINVASIVE TECHNIQUES FOR ASSESSMENT OF MYOCARDIAL

STIFFNESS BY ECHOCARDIOGRAPHY

C. Pislaru

Mayo Clinic College of Medicine, Rochester, Minnesota, USA

Structural changes in the tissue brought by the disease (e.g., cancer, liver cirrhosis and fibrosis,

myocardial infarction, heart failure, etc.) alter biomechanical properties of the tissue (elasticity and

viscosity). Increasing evidence exists that measurement of tissue elasticity by ultrasound and

magnetic resonance imaging can detect such alterations in liver, breast, thyroid, and prostate. The

assessment of myocardial stiffness has been more challenging to achieve, and remains restricted

to invasive techniques (pressure-volume measurements in the catheterization laboratory). Recent

developments suggest that noninvasive estimation of myocardial elasticity by ultrasound and

magnetic resonance imaging may be clinically possible in the near future. We recently introduced

a new method that relies on analysis of intrinsic myocardial waves to estimate myocardial elasticity

during diastole. This technique has been validated in animal studies, demonstrating that

myocardial wave speed was highly correlated with the stress-strain derived elastic modulus

measured by gold-standard invasive techniques. We have used this wave-based technique in >100

patients with various cardiac diseases. The results indicate that intrinsic myocardial wave speed is

altered in left ventricular myocardium of patients with severe aortic stenosis, cardiac amyloidosis,

heart failure with preserved ejection fraction, and hypertrophic cardiomyopathy compared to age-

matched healthy subjects. Less severe changes were found in patients with degenerative severe

mitral regurgitation. Preliminary results suggested that a higher wave speed was associated with

reduced exercise capacity and peak myocardial oxygen consumption. Noteworthy, the wave speed

measured by the intrinsic wave method was comparable to the shear wave speed produced by the

ultrasound radiation force which is more challenging to apply effectively throughout the left

ventricle at transthoracic imaging. In conclusion, measurement of myocardial stiffness has

potential to become a new noninvasive imaging biomarker that may help with identification of

structural changes in the myocardium caused by the disease.

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018

COMPUTED TOMOGRAPHY CORONARY ANGIOGRAPHY: DIAGNOSTIC AND

PROGNOSTIC VALUE

F.B. Sozzi

Cardiology Unit, Policlinico Hospital, Milan, Italy

Monaco Cardiothoracic Centre, Monaco, Monaco

Coronary multislice computed tomography (CT) is increasingly being used as a tool for non-

invasive visualization of the coronary arteries (1). The technique provides information on

atherosclerotic plaque burden and to some extent on plaque composition. The diagnostic value of

coronary CT scan is high. In the last few year a flourish literature on the prognostic value of

coronary CT has been published. Accuracy of coronary CT needs to be assessed in management

outcome studies, in which diagnostic and therapeutic strategies would be decided based on CT

alone, without reference to any coronary angiography results.

A main point is that plaque composition represents a long-term predictor of cardiac events. In a

long-term follow-up study on the predictive value of coronary CT, Sozzi et al (1) demonstrated

that non-calcified and mixed plaques carried a worse prognosis compared to calcified plaques.

Referring to plaque vulnerability concept, Mann et al (2) studied 31 subjects who died suddenly

of CAD. They found that lipid core size and minimal cup thickness, 2 major determinants of

plaques vulnerability, were not related to absolute plaque size or degree of stenosis. Accordingly,

atherosclerotic plaque growth and destabilization are highly variable. Many serial angiographic

studies have demonstrated that most AMI occur due to the occlusion of coronary arteries that did

not previously contain significant stenosis; furthermore the coronary artery with the most severe

stenosis is usually not the “culprit” one. Thus, plaque progression and clinical outcome are not

always closely related, and each is poorly predicted on clinical and angiographic grounds, as most

plaques that underlie an AMI are <70% stenosed.

Previously, CT was associated with elevated radiation exposure. Radiation doses are rapidly

decreasing with newer acquisition protocols, arriving to an exposure of 2 mSv per exam.

1. Sozzi FB, Civaia F et al. Long-term follow-up of patients with first-time chest pain having 64-

slice computed tomography. AJC 2011;15:516-21.

2. Mann JM, Davies MJ. Vulnerable plaque. Relation of characteristics to degree of stenosis in

human coronary arteries. Circulation 1996;94:928-931.

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019

EXERCISE ECHOCARDIOGRAPHY: ADVANTAGES AND DISADVANTAGES

M. Prokudina

Federal North-West Medical Research Center, St. Petersburg, Russia

The presentation will describe the advantages and disadvantages of exercise echocardiography (Ex

Echo) for evaluation of coronary artery disease (CAD). Advantages and benefits of Ex Echo are

the following:

1. Accuracy and availability;

2. Test is non-invasive (Ex Echo avoids the risks of invasive procedures) and inexpensive;

3. Ex Echo does not require the purchase, handling or disposal of radionuclides;

4. Ex Echo provides real-time global and regional information about the ventricles;

5. The resting echo also provides additional information about valvular disease, site and extent of

MI, chamber dilatation, thrombi and aneurysm;

6. Ex Echo is convenient to clinical practice, it takes less time, can be scheduled immediately and

can be scheduled any time during a day;

7. Stress echo requires minimal staff.

Disadvantages of stress echocardiography are the following:

A. Factors contributing to false positives: severe hypertension, cardiomyopathies (LV dysfunction

of unknown etiology), idiopathic hypertrophic subaortic stenosis; left bundle branch block,

arrhythmias, pacemaker; severe AI; insufficient level of exertion; reader is too sensitive to very

mild hypokinesia and over-reading normally stiff segments.

B. Factors contributing to false negatives: single-vessel disease, normalization of wall motion

abnormalities, extensive collaterals to occluded vessel, the influence of medications, resting wall

motion abnormalities and technical problems.

Conclusion: In spite of some false-negative and false-positive tests accuracy of exercise

echocardiography is high and it is an excellent tool for evaluation of CAD.

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020

POINT OF CARE ULTRASOUND, THE NEW PHYSICAL EXAMINATION I. Kedan1, R. Khandwalla1, M. Ciozda2

1. Cedars Sinai Heart Institute, Los Angeles, CA, USA

2. UCLA Medical School, Los Angeles, CA, USA

Background: Ultrasound technology has become a central part of modern day healthcare. Its use

as a clinical tool will continue to expand as the technology becomes more portable.

Hypothesis: Point-of-care (POC) ultrasound will ultimately replace the prior medical paradigm of

a physical examination centric approach to patient evaluation.

Limitations: 1. Cost of equipment 2. Access to devices 3. Reimbursement model for use of

technology 4. Learning curve and scarcity of master clinician ultrasound educators 5. Legal

barriers and potential regulatory barriers.

Methods for adoption: 1. Change reimbursement model to deliver population based care to include

bundling of reimbursement 2. Engage new device delivery models that allow access to equipment

with a lower cost of entry 3. Build in ultrasound curricula to all levels of medical and clinical

training 4. Expand the Emergency Department model of standardized examinations (FAST scan)

into focused systems based examinations for point-of-care hypothesis testing.

Possible initial strategies: 1. Start with specific actionable evidence based imaging (IVC, gall

bladder, pleural effusions) 2. Enlist medical training programs to incorporate POC ultrasound into

all facets of curricula 3. Expand users of POC ultrasound to health care extenders and ancillary

health care professionals to acquire actionable imaging data for physicians remotely.

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021

DO PELVIC VASCULAR BED CALCIFICATIONS CORRELATE TO CORONARY

ARTERY CALCIFICATIONS IN MODERN AMERICAN POPULATION? K. Palatnik1, M.J. Budoff2, M. Kim2, D.S. Berman1, J. Mirocha1, Y. Charuzi1

1. Cedars-Sinai Medical Center, Los Angeles, CA, USA

2. Harbor-UCLA Medical Center, Torrance, CA, USA

Background: In recent years, computed tomographic (CT) assessment in ancient mummies

revealed aortoiliac calcifications thought to represent atherosclerosis, challenging the assumption

that atherosclerosis is a modern disease. In an effort to characterize the presence of atherosclerosis

in the often incomplete anatomy of mummies, we sought to investigate the correlation of pelvic

vascular calcifications to the presence of coronary calcifications. A study in modern Egyptians

revealed that atherosclerotic calcifications seen in aortoiliac beds preceded the appearance of

coronary calcifications by almost a decade. The goal of our study was to investigate a correlation

between iliac and coronary artery calcifications in modern population.

Methods: We randomly selected 103 patients (64% male) who underwent screening body CT.

Mean age was 57 +/- 11 years (range 31-84). Using these scans, coronary, right and left iliac artery

calcifications were quantitatively assessed.

Results: Results revealed that coronary and iliac artery calcification scores correlated with age (p<

0.0001), but not BMI or BSA. The right iliac (54 of 103) and left iliac (51 of 103) artery

calcifications correlated with each other (r = 0.745, p<0.0001). The total coronary calcification

score correlated with both left (r = 0.590, P < 0.0001) and right (r = 0.679, P < 0.0001) iliac scores.

Further analysis using the Fisher exact test revealed coronary calcification in 76.5% (39 of 51) of

those with left iliac calcification, 79.6% (43 of 54) of those with right iliac calcification and 82.9%

(34 of 41) of those with bilateral iliac calcification. In those without iliac calcifications, 30.8% (12

of 39) had coronary calcifications.

Conclusion: The presence of iliac calcifications is suggestive of coronary calcifications. However,

the absence of iliac calcifications does not preclude coronary calcifications.

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INTERVENTIONAL CARDIOLOGY / ANTITHROMBOTIC AND ANTIPLATELET THERAPY IN PCI

022

UPDATE ON THE TREATMENT OF THE CHRONIC TOTAL OCCLUSION

B. Uretsky

University of Arkansas for Medical Sciences, Little Rock, AR, USA

A key goal in treating obstructive coronary disease is complete revascularization (CR). Multiple

observational and registry studies have suggested the value of CR in maximizing survival,

minimizing long-term adverse cardiac events, and improving the quality of life. The primary

challenge to providing CR with percutaneous intervention (PCI) is treatment of the chronic total

occlusion (CTO). Because of the technical challenges, the CTO is often ignored in PCI treatment

citing the presence of collaterals filling the region and suggesting that the CTO is a rather “benign”

lesion. The idea that collaterals adequately perfuse the myocardium in the CTO territory is a myth;

that area is, in fact, a chronically ischemic zone and may account for the worsened outcome of

CTO patients compared with matched non-CTO CAD patients. CTO PCI should align with

guidelines and appropriate use criteria for management of the non-CTO lesion, governed by the

same criteria, i.e. the extent of symptoms and ischemia and the adequacy of medical therapy.

Available data have shown that revascularization with PCI of a CTO can improve symptoms,

decrease the need for bypass surgery and improve ventricular function and may improve survival.

Newer techniques have improved recanalization rates from the relatively poor 60-70% range as

reported in large registries to the current 90% range in centers of excellence. These techniques

include the antegrade dissection-re-entry technique with dedicated tools including the CrossBoss

catheter, Sting-Ray balloon, and Sting-Ray re-entry wire and retrograde techniques, both intra-

luminal and dissection re-entry. Currently no randomized trials have demonstrated that CTO PCI

is more effective than medical therapy or bypass surgery in multivessel disease but such trials are

ongoing and should provide increased clarity in decision-making.

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023

A CONTEMPORARY PRACTICE PATTERN AND OUTCOME FOLLOWING

TRANSRADIAL AND TRANSFEMORAL INTERVENTIONS IN RECENT

ANTIPLATELET ERA: A PROPENSITY SCORE-MATCHED ANALYSIS K.S. Cha1, J.C. Choi1, J.H. Choi1, B. Kim1, J.S. Park1, H.W. Lee1, J.H. Oh1, H.C. Lee1, T.J.

Hong1, J. Yoon2

1. Pusan National University Hospital, Busan, South Korea

2. Yonsei University Wonju Severance Christian Hospital, Wonju, South Korea

Purpose: Radial artery is an access site for percutaneous coronary intervention. We compared

clinical outcomes after transradial intervention (TRI) and transfemoral intervention (TFI) in

contemporary antiplatelet era.

Methods: Among 6,973 patients enrolled in a nationwide, prospective, multicenter registry from

February to September 2013, eligible 1,860 patients were divided into TRI (n=1,445, 77.7%) and

TFI (n=415, 22.3%) groups based on the vascular access site. Bleeding and major adverse cardiac

events (MACE; death, recurrent myocardial infarction, revascularization, or stent thrombosis)

were compared. Propensity score (PS)-matched analysis was performed in 728 patients.

Results: TRI group had significantly lower bleeding rate than TFI group in the entire (1.5% vs.

4.8%, odds ratio [OR] 0.38, 95% confidence interval [CI] 0.19–0.78, p=0.008) and PS-matched

(2.7% vs. 5.2%, OR 0.42, 95% CI 0.19–0.94, p=0.035) cohorts. In multivariate regression, TRI

was associated with bleeding in the entire (odds ratio [OR] 0.381, 95% confidence interval [CI]

0.186–0.781, p=0.008) and PS-matched (OR 0.424, 95% CI 0.191–0.942, p=0.035) cohorts.

Kaplan-Meier estimates showed that MACE-free survival was higher in TRI group than TFI group

in the entire (93.3% vs. 87.5%, log rank p=0.026) and PS-matched (91.8% vs. 87.1%, log rank

p=0.04) cohorts. In Cox proportional hazard analysis, TRI was an independent predictor of MACE

in the entire (hazard ratio [HR] 0.65, 95% CI 0.45–0.93, p=0.02) and PS-matched (HR 0.61, 95%

CI 0.39–0.96, p=0.034) cohorts.

Conclusions: This study showed that TRI was associated with a reduced bleeding rate and better

clinical outcomes compared to TFI in contemporary real-world practice.

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024

UTILITY OF FREQUENCY DOMAIN OPTICAL COHERENCE TOMOGRAPHIC

EVALUATION OF ANGIOGRAPHICALLY OPTIMIZED STENTED LESIONS M. Agrawal, Z. Ahmed, A. Hakeem, B.F. Uretsky

Central Arkansas Veterans Health System and the University of Arkansas for Medical Sciences,

Little Rock, AR, USA

Purpose: Optical coherence tomography (OCT), given its high resolution, may be a useful clinical

tool to optimize stent deployment. We evaluated the nature and frequency of post-stent deployment

OCT findings prompting further intervention.

Methods and Results: We evaluated 100 patients (pts), 127 stents, and 127,894 stent struts with

post-PCI OCT who had angiographically optimized coronary stent implantation: 44% with

unstable angina/NSTEMI, pre-PCI diameter stenosis 81±16%, stent diameter 3.0±0.4 mm, length

24.7±10.3 mm. Post-PCI in-stent minimal lumen area was 6.6±2.4 mm2 and minimal lumen

diameter 2.7±0.5 mm. OCT findings were classified as ‘significant’ if an OCT finding prompted

further intervention. Specific findings on OCT are summarized in table below. OCT findings

were considered significant in 50 pts (50%), requiring the following interventions: 78% further

balloon dilatation, 14% another stent implantation 6% treatment with Gp IIb/IIIa inhibitors, and

2% aspiration thrombectomy.

Conclusions: Post-PCI OCT was helpful in improving stent deployment in half the studied cases.

Inappropriate angiographic stent sizing was the most common reason for significant OCT findings

prompting further treatment. This finding recommends pre-PCI OCT when feasible when feasible.

Overall results suggest the value of OCT in optimizing stent deployment.

Table 1: Abnormalities Found on Post-PCI OCT

Abnormality Percentage of Patients (%)

Any abnormality 73

Malapposition 44

Stent underexpansion 12

Plaque prolapse 9

Thrombus 6

Angiographically unrecognized lesion 5

Uncovered dissection flap 4

Other (lesion ulcer, calcification) 2

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025

LONG TERM CLINICAL OUTCOMES FOLLOWING SIROLIMUS-ELUTING STENT

IMPLANTATION IN DIABETIC VS. NON-DIABETIC PATIENTS L. Mimish1, A. Khoja2, N. Ahmad1, I. Altnji1, H. Mimish1, B. Khambhati3, A. Thakkar3

1. King Abdulaziz University, Jeddah, Saudi Arabia

2. King Fahad MOH Hospital, Jeddah, Saudi Arabia

3. Sahajanand Medical Technologies Pvt. Ltd., Surat, Gujarat, India

Objective: Objective of this registry was to compare the long term clinical outcomes of the

Supralimus-Core sirolimus-eluting stent (SES) in complex, non-selected diabetic and non-diabetic

patients.

Background: Drug-eluting stents (DES) reduce restenosis and target lesion revascularization

(TLR) in both diabetic and non-diabetic patients. However, there are limited data on the long term

safety and efficacy of DES in diabetic patients.

Methods: Between April-2008 and May-2014, 500 patients treated exclusively with biodegradable

polymer-coated Supralimus-Core SES (Sahajanand Medical Technologies Pvt. Ltd., Surat, India)

were consecutively enrolled in the non-randomized, observational, multicenter SCODA registry.

Of these, 269 patients were diabetic, whereas 231 had non-diabetic. Primary endpoint was long-

term combined major adverse cardiac events (MACE) including death, myocardial infarction (MI),

TLR, target vessel revascularization (TVR)/ coronary artery bypass graft (CABG) and stent

thrombosis. Clinical follow-up was obtained up to 6 years. Mean follow-up time was 4.0±1.8 years

(range, 3 to 6 years) and was achieved in 64.6% (323/500) of patients.

Results: A total of 500 patients, with mean age of 55.1±10.4 years, were included in this registry.

Diabetic patients had a higher prevalence of arterial hypertension (60.2% vs. 40.3%, p<0.001),

hypercholesterolemia (72.1% vs. 41.1%, p<0.001) and unstable angina (41.6% vs. 29.4%,

p=0.005) compare to non-diabetic patients. During 6 years follow-up, the cumulative incidence of

MACE in patients with diabetes was comparable to that of non-diabetics [19 (7.1%) vs. 27

(11.7%), p=0.074]. The diabetic patients demonstrated a higher, but non-significant, incidence of

TVR/CABG compared to non-diabetic patients [7 (2.6%) vs. 5 (2.2%), p=0.750]. The incidence

of stent thrombosis was similar between diabetic and non-diabetic patients [1 (0.4%) vs. 0 (0),

p=1.000)].

Conclusion: Despite complex lesion morphology, this multicenter registry demonstrates

satisfactory and sustained six years clinical outcomes as evidenced by the low rates of MACE, for

the Supralimus-Core SES, in diabetic and non-diabetic patients.

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026

FERROMAGNETIC STENT-GRAFT FOR RAPID ENDOTHELIAL CELL-CAPTURE

S. Uthamaraj1, B.J. Tefft2, G.S. Sandhu2,3, D. Dragomir-Daescu1,3 1Division of Engineering, 2Division of Cardiovascular Diseases, 3Mayo Clinic College of

Medicine, Rochester, MN, USA

Objectives: Develop a stent-graft by combining electrospun polyurethane nano-fibers and a

ferromagnetic stent to enhance endothelial cell-capture and retention.

Background: Stents-grafts are an important advancement in vascular interventions, but restenosis,

thrombosis and distal embolism continue to be concerning issues. Stent-grafts were originally

developed by sandwiching a polymer between stents. In this study, we have developed a stent-

graft in which a ferromagnetic stent was encapsulated between 2 layers of polymer thereby

becoming capable of capturing and retaining magnetically-labeled endothelial cells to promote

healing.

Methods: An electrospinning system was developed for creating nano-fibers from medical-grade

polyurethane (BioSpan®, DSM, Exton, PA). First, nano-fibers were electrospun on a 3mm

diameter rotating mandrel to form a graft. Next, a previously developed ferromagnetic stent made

from 2205 stainless-steel was placed on the graft and electrospinning was continued to form the

outside layer. We manufactured 7 stent-grafts and inspected them microscopically for surface and

construct integrity. Three of the stent-grafts were tested for crimping and expansion to verify

mechanical competence. Finally, one stent-graft was tested in-vitro for endothelial cell-capture.

Results and conclusions: The stent-grafts developed in this study (Fig1a) were suitable for

deployment using a standard trifold balloon (Fig1b,c). Microscopic evaluation showed that the

electrospun fibers sandwiched the stent without any observed delamination between layers due to

manufacturing and after deployment. Using fluorescence imaging, the magnetized stent-graft

proved to attract and retain magnetically-labeled cells in-vitro (Fig1d, cells appear white). Thus,

our proof of concept stent-graft showed promise for targeted cell seeding which can facilitate rapid

healing.

Figure1

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027 RADIAL APPROACH TO CORONARY ARTERY BYPASS GRAFT ANGIOGRAPHY AND

INTERVENTION REDUCES ACCESS SITE COMPLICATIONS Y.R. Manda, S. Agrawal, C. Sarnoski, R. Durkin, P. Puleo, J. Shirani

St Lukes University Health Network, Bethlehem, PA, USA

Background: Transradial (TR) approach to coronary artery angiography and intervention is gaining

popularity with reduced morbidity and mortality compared to transfemoral (TF). Safety and effectiveness

of TR approach in setting of bypass graft angiography and intervention is not well studied.

Methods: Systemic review of literature identified 1 randomized and 6 observational studies (n=1370) that

addressed this issue. Meta-analysis compared characteristics and outcomes of each approach including

vascular access site complications, major adverse cardiovascular events (MACE), access site crossover

rates, fluoroscopy time, procedure time and contrast volume use.

Results: (figure). Baseline patient characteristics were similar in both groups. Compared to TF, TR had

decreased vascular access site complications (1.4%-vs-3.8%; OR: 0.34, 95% CI 0.16-0.75; p=0.008) and a

tendency towards lower MACE (2.39%-vs- 4.7%; OR 0.57, 95% CI 0.25-1.3; p=0.18). No difference was

found in rates of major bleeding (0.17%-vs-0.57%; p=0.58) or in-hospital death (0.29%-vs-0.7%, p=0.54).

Risk of vascular access site crossover was higher in TR (5.16%-vs-0.4%; p=0.0003). TR was associated

with comparable fluoroscopy time, procedure time and contrast volume usage to TF (all p>0.05).

Conclusion: Transradial approach to bypass graft angiography and intervention reduces vascular access

site complications and has comparable fluoroscopy time and contrast volume usage.

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028

RELATIONSHIP OF INTRA-PROCEDURAL HEPARIN DOSE AND ACTIVATED

CLOTTING TIME DURING PERCUTANEOUS CORONARY INTERVENTION

K. Narala, S. Banga, H. Ghadiam, D. Narala, T. Grewal, A. Aggarwal, A. Akepati,

S. Mungee

Department of Cardiology, University of Illinois College of Medicine at Peoria, Illinois, USA.

Background: Heparin dosing is done at physician discretion during percutaneous coronary

intervention (PCI).

Objectives: We aim to describe the effect of unfractionated heparin dosing on intra-procedural

activated clotting times (ACT).

Methods: Retrospective analysis was performed of 70 patients who presented as ST elevation

myocardial infarction (STEMI) and underwent PCI. Patients were given initial bolus of

intravenous heparin on presentation. First ACT was recorded in the catheterization lab on arrival.

Additional intra-procedural doses of heparin were at the discretion of the physician and second

ACT level was recorded. The use of glycoprotein IIb/IIIa inhibitor was at the discretion of the

physician. Nominal and continuous data were analyzed. Mean and standard deviations were

calculated.

Results: Patient population was 74% male, 69% hypertensive, 26% diabetic and 56% smokers.

Initial dose of approximately 50 IU/kg of unfractionated heparin (UFH) lead to first ACT time of

192 sec, 28 min after administration. Repeat dosing of 25 IU/kg lead to an ACT of 240 sec,

approximately 25 min after administration.

Conclusion: Current guidelines emphasize weight based initial dosing of heparin for percutaneous

coronary intervention. However, there is a lack of guidelines for subsequent heparin dosing.

Heparin nomograms should be encouraged to help maintain appropriate therapeutic

anticoagulation during PCI.

Table 1.

Parameter Value

Mean age 59.5±11.9 yrs

Mean weight 86.6±18 kg

Average First heparin bolus/kg 49±10 IU/kg

Mean Time to First ACT check 28±2.5 min

Mean First ACT 192±26 sec

Percent of patients with First ACT less than 250 sec (N) 97% (68/70)

Average Second heparin bolus/kg 25 ±14 IU/kg

Mean time to Second ACT check 25.5±13.5 min

Mean Second ACT 240±57 sec

Percent of all patients with Second ACT less than 250 sec. (N) 61% (43/70)

Percent of patients on GPIIb/IIIa inhibitors (N) 53% (37/70)

Percent of patients on GPIIb/IIIa inhibitors with second ACT<250sec (N) 59% (22/37)

Percent of patients on UFH only during the PCI (N) 47% (33/70)

Percent of patients on UFH only during PCI and second ACT<250sec (N) 61% (20/33)

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PEDIATRIC CARDIOLOGY AND CARDIAC SURGERY, CONGENITAL HEART DISEASE

029

RIGHT ATRIAL MECHANICS PROVIDE USEFUL INSIGHTS IN IDIOPATHIC

PULMONARY HYPERTENSION IN CHILDREN

K. Hope, Y. Wang, H. Nawaytou, B. Hanna, A. Banerjee

Children's Hospital of Philadelphia, Philadelphia, PA

Background: Identification of impending right ventricular (RV) decompensation is inaccurate in

children with idiopathic pulmonary hypertension (PH), since 6-minute walk distance and degree

of tricuspid regurgitation (TR) do not deteriorate with increase in disease severity, as in adult PH.

In absence of TR, current echo indices are poor predictors of disease severity. Right atrial (RA)

mechanics may provide insight into state of RV compensation.

Methods: 16 patients (age 3-20 years) with severe PH but without significant TR and 12 matched

controls were studied. RA longitudinal strain (RALS) & longitudinal displacement (LD) were

calculated by speckle-tracking echocardiography. Area enclosed by RALS-LD loop measured

atrial "work". RV area-change (RVAC) and tricuspid annular plane systolic excursion (TAPSE)

served as indices of RV function. Mean pulmonary artery pressures (mPAP) were available within

6 months. RALS >40% was used to distinguish compensated from decompensated PH.

Results: mPAP & RALS showed significant correlation (r=0.71). RALS-LD loop area was

preserved in compensated PH, but drastically reduced in decompensated PH (Figure 1). Defining

RV decompensation as a state of low RALS allowed identification of a subgroup of PH patients

with higher mPAP and lower TAPSE and RVAC.

Conclusions: RALS can identify both increasing mPAP and RV deterioration and may detect

decompensation in pediatric PH.

Figure 1

Table 1: Right Heart Data

mPAP (mm Hg) RALS (%) Loop Area (u) TAPSE (cm) RVAC (%)

Normal 55.59 ± 6.99 46.03 ± 31.49 1.96 ± 0.33 51± 9

Compensated 51.38 ± 8.25 56.74 ± 14.33 39.69 ± 20.64 1.72± 0.49 42± 14 *

Decompensated 81.57 ± 18.28 26.10± 18.62 *¶ 12.97 ± 31.83 *¶ 1.53± 0.51 * 25 ± 12 *¶

(mean ± SD, * p<0.05 when compared with normal, ¶ p<0.05 decompensated versus compensated state. Newman-Keuls test

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MORPHOLOGIC SEVERITY DOES NOT PREDICT MYOCARDIAL CONTRACTILE

FUNCTION IN PEDIATRIC NONCOMPACTION CARDIOMYOPATHY C. Lilje, J.C. Cronan, K. Leone, O. Evrim, S. Patel

Louisiana State University Health Sciences Center, New Orleans, LA, USA

Objectives: To evaluate in a pediatric population whether morphologic Noncompaction

Cardiomyopathy (NCC) severity correlates with left ventricular contractile function.

Background: NCC is a likely under-diagnosed developmental disorder defined by morphologic

criteria. It is associated with a high morbidity and mortality, mostly due to poor contractile

function. Predictive markers have not yet been identified.

Patients and methods: 58 patients (age 6.2±6.7 years, 33% females) were diagnosed with NCC

between 4/2006 through 4/2014 and qualified for retrospective analysis. 16 (29%) patients had

associated congenital heart defects (CHD). NCC severity was graded by the number of cardiac

segments affected as mild (<6), moderate (6-11), and severe (>11). Low left ventricular contractile

function was defined echocardiographically by an ejection fraction (EF) <56%.

Results: NCC was mild, moderate, and severe in 27 (46%), 26 (45%), and 5 (9%) patients. EF was

low in 19 (33%) patients. Patients with low EF were not different from patients with preserved EF

in regard of age, weight, gender, associated CHD, or morphologic NCC severity. EF was low in

10 (37%) patients with mild NCC, 7 (27%) patients with moderate NCC, and 2 (40%) patients

with severe NCC (p=0.37). Four patients (7%) required mechanical circulatory support or heart

transplant; two patients (3%) died. Only one of these six patients (10%) was at high risk by

morphologic severity criteria.

Conclusion: Morphologic NCC severity does not predict left ventricular contractile function in a

pediatric population. Predictive functional markers for NCC are still urgently needed.

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031

TRANSCATHETER CLOSURE OF PERIMEMBRANOUS VENTRICULAR SEPTAL

DEFECT A. Lorber, M. Dotan, Y. Or

Department of Pediatric Cardiology and Adults with Congenital Heart Disease, Ruth Children's

Hospital, Rambam Health Care Campus, The Rappaport Faculty of Medicine – Technion, Haifa,

Israel

Background: Surgical closure is still considered as the most common treatment for significant

perimembranous ventricular septal defects. Although perioperative mortality and morbidity rates

became very low with advanced surgical techniques and improved postoperative management, this

approach still carries the risks and complications of open heart surgery with cardio-pulmonary

bypass. The transcatheter approach offers a valuable less invasive alternative with shorter hospital

stay. Periprocedural complications include atrioventricular block - which reduced the popularity

of the procedure, residual shunt, infective endocarditis and hemolysis. The NitOcclud Le coil

initiates a revolutionary initiative that overcomes the atrioventricular conduction concern.

Objective: Assessing the efficacy, safety, short and long term results and complications of

percutaneous closure of perimembranous ventricular septal defects using the Nitocclud Le VSD

coil.

Methods: Twenty nine patients (17 F: 12 M; mean age 12 years, range 3-36 years) underwent

transcatheter coil closure of perimembranous ventricular septal defects between May 2009 and

November 2011. Success rate, adverse events, short and long term complication are reported. Multi

variant analysis was performed to identify risk factors, positive and negative independent

predictors.

Results: The success rate was 96.5% (28/29 procedures). Minor and transient short term

complications were 31%, comprising coil related hemolysis, femoral artery thrombosis, catheter

induced second degree atrioventricular and fascicular block. Two patients experienced major

complications which required surgical intervention. One patient presented with late onset Kingiella

Kingii endocarditis 6 months after the procedure and the second patient developed progressive

tricuspid regurgitation. No long term atrioventricular block was observed by repeated ECG and

ECG holter studies.

Conclusions: The transcatheter approach using the NitOcclud Le coil for the closure of

perimembranous ventricular septal defect may be an effective and safe alternative to surgery.

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PEDIATRIC POST-OPERATIVE ATRIO-VENTRICULAR BLOCK MEETS THE

AFFORDABLE CARE ACT: A NEW STRATEGY FOR MANAGEMENT M.L. Morello1, J.S. Steinberg2, C. Snyder1

1.. Division of Pediatric Cardiology, Rainbow Babies & Children’s Hospital, Case Western

Reserve University School of Medicine, Cleveland, OH, USA

2. School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA

Introduction: Post-operative (post-op) complete atrio-ventricular heart block (CAVB) occurs after

approximately 1-4% of pediatric cardiac operations. Current practice dictates implantation of

permanent pacemaker (PPM) when post-op CAVB persists > 9 days. We propose that earlier PPM

implantation may be the most cost-efficient methodology of caring for these patients since patient

costs increase with extended length of stay (LOS).

Methods: Data on the probabilities of persistent post-op CAVB were extracted from published

reports. This was utilized to create a decision-making model and a total cost analysis on post-op

day 0-10 to determine the most cost-efficient day to implant a PPM. Cost variables included

estimates of daily cardiac ICU care, cost of PPM implantation, LOS, cost related to possible

superficial or deep infection based on published prevalence rates (2.3% and 4.9%, respectively)

and need for explant due to deep infection or recovery of native conduction. The model assumes

5-day minimum LOS and 1 day increase in LOS with PPM implantation. Cost data were obtained

from relevant billing codes and manufacturer list prices for PPM and leads. A secondary analysis

evaluated probability of unnecessary PPMs implanted and excess costs.

Results: Post-op day (POD) 4 is the lowest total cost of PPM implantation for post-op CAVB, even

when accounting for possible risk of either superficial or deep infection. A one-way sensitivity

analysis accounting for variability of cardiac ICU care costs between centers ranging from $3,000-

$9,000 per day consistently replicates POD 4 as the most cost-effective day for PPM implantation.

Implant on POD 4 results in a 26% chance of unnecessary implantation.

Conclusions: The most cost-efficient day for PPM implantation for post-op CAVB is post-op day

4, which results in a minimum total cost savings of $17,422 per patient. Added costs due to risk

of superficial or deep infection are marginal due to low prevalence of post-operative infection in

this population.

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033

HEART FAILURE CRT PACING IN CONGENITAL HEART: ACUTE VENTRICULAR

PACED CONTRACTILITY (DP/DT) IS AN EFFECTIVE MARKER TO PREDICT

CHRONIC EFFICACY P.P. Karpawich, Y. Sanil, N. Bansal, K. Zelin

The Children's Hospital of Michigan/Wayne State University, Detroit, MI, USA

Introduction: Patients (pts) with congenital heart disease (CHD) often develop heart failure (HF).

Cardiac resynchronization pacing therapy (CRT) may improve HF. However, published pt

selection criteria, including ejection fraction (EF) <35%, may not apply as EF is often inaccurate

in many CHDs as well as pts with pacemakers (PM). This study evaluated acute ventricular (V)

paced contractility (dP/dt) response pre-CRT implant to determine chronic CRT efficacy among

CHD pts with HF.

Methods: Data from CHD pts being listed for heart transplant (HT) who underwent catheterization

studies with temporary bi-V CRT-paced hemodynamics were reviewed. Positive CRT benefit was

defined as >15% increase in dP/dt over baseline. Pts were given the option of CRT in addition to

standard HF medical therapy and followed (2-144 months, mean 34) for outcome.

Results: EF could accurately be measured in only 20/32 pts (62%) measuring 16-62% (mean 35%).

A positive CRT benefit was found in 22/32 pts (mean 22y age), 15/22 with preexisting PM (mean

dP/dt increase from 551 to 823mmHg-sec, p<0.006). All 22 pts received CRT implant. During

follow-up, all improved in NYHA class with improved HF symptoms and EF (36% vs 52%, p <

0.01) compared with pre-CRT values. Of these pts, 4 underwent HT (mean 56 mos later), 3 died

(2 noncompliance (NC)) and 15 remain stable (NYHA class 1-3), off the HT list (repeat dP/dt

mean 843mmHg-sec). Of the 10 pts with a negative CRT response (mean dP/dt 635 vs 662mmHg-

sec, p=NS), 2 received HT (mean 12 mos later) and both died within 6y post HT, 2 died awaiting

HT (NC), and 6 remain on the HT list (NYHA 2-4).

Conclusions: Pt response to CRT is often equivocal. Pre-selecting CHD pts by direct acute paced

contractility (dP/dt) response assures greater CRT efficacy, can delay need for HT and improve pt

well-being.

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034

ABNORMAL FETAL Z-SCORES ARE A SENSITIVE PREDICTOR OF FETAL

CONGENITAL HEART DISEASE C.A. Albaro, R.G. Shah, K.F. Welke, A.M. Duncan, J.J. Shah, M.T. Bramlet

Children's Hospital of Illinois, Peoria, IL, USA

Introduction: Current obstetric fetal cardiac screening recommendations fail to provide the proper

tools necessary to accurately identify congenital heart disease (CHD). We sought to utilize 4

established normative fetal measurements to simplify screening for CHD. Hypothesis: Abnormal

z-scores of 4 fetal cardiac measurements are a sensitive predictor of CHD.

Methods: We performed a retrospective review of fetal echocardiograms done on neonates with a

post natal diagnosis of CHD from 2010 to 2013. Four anatomic measurements (aortic annulus,

pulmonary valve annulus, right and left ventricular diameters) were performed according to ASE

guidelines and compared to normative z-score reference ranges from published data. CHD lesions

were categorized as right-sided lesions (tetralogy of Fallot, tricuspid and pulmonary valve

abnormalities), left-sided lesions (hypoplastic left heart syndrome, aortic valve abnormalities,

aortic coarctation and interrupted aortic arch), transposition of the great arteries (TGA), ventricular

septal defects (VSD), and atrioventricular septal defects (AVSD).

Results: 120 patients with average gestational age of 28.2 weeks met criteria. At least 1 abnormal

z-score was present in 93 of 120 patients. Overall sensitivity was 78 percent but varied by lesion

subgroups. Sensitivity was lowest for VSD (53 percent), AVSD (62 percent) and simple TGA (33

percent) and highest for right sided lesions, left sided lesions and complex TGA. When VSD,

AVSD and simple TGA were removed from the cohort, sensitivity improved to 90 percent.

Conclusion: Abnormal fetal z-scores are a sensitive predictor of CHD. Inclusion of z-scores of 4

fetal cardiac measurements in level 1 obstetric sonograms can identify patients needing referral

for fetal echocardiography and improve detection rate of CHD. Additional focus on TGA and

septal defects would further improve detections rates.

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035

PRENATAL DIAGNOSIS AND OUTCOMES OF FETUSES WITH TRICUSPID

ATRESIA IN A COUNTRY WITH LIMITED RESOURCES R. Bejiqi1, R.J. Retkoceri1, H.S. Bejiqi2, A.S. Beha2, A.R. Retkoceri1

1. Pediatric Clinic Universitu, Clinical Center of Kosovo, Prishtina, Republic of Kosovo

2. Mean Center of Family Medicine, Prishtina, Republic of Kosovo

Aim of this presentation was retrospective analysis of diagnosis, features and outcomes of fetuses

with TrA diagnosed in our clinic.

Method and material: Between January 2001 and December 2012 were studied around 326 fetuses

with congenital heart diseases; in 23 (7.0%) were found TrA. Age of gestation at time of diagnosis

was 16 -38 weeks gestation. Retrospectively were analyzed characteristics and outcomes of 18

cases with known follow-up.

Results Characteristics: Three fetuses were twins, 2 fetuses were triple. Five fetuses (21.7%) had

restrictive interatrial communication and balloon atrioseptostomy immediately were performed.

Twelve of them had heart failure already at presentation, due to restrictive communication. All

fetuses had nonrestrictive VSD, 5 of them had additional muscular restrictive VSD. Five fetuses

(17.4%) had transposition of great arteries with nonrestrictive VSD, 8 fetuses (34.8%) had

pulmonary stenosis, 2 (8.7%) had pulmonary atresia, 9 were (39.1%) with patent ductus, one with

aortic coarctation, 6 had associated extracardiac anomalies.

Outcomes: Seven pregnancies (30.4%) were terminated, 6 with extracardiac anomalies. Out of 16

fetuses that continued pregnancies, 3 died in utero, 3 died shortly after birth and 3 died in second

month of live waiting for surgery. The remaining 10 cases were operated with palliative procedures

and latter underwent surgery (Glenn/Fontan procedure). Total intrauterine and postnatal mortality

was 16/23 (69.6%).

Conclusion: Despite of improvement perinatal diagnosis management and outcomes of fetuses and

children with TrA in Kosovo remain still poor. Negative prognostic factors were restrictive atrial

communication, long term waiting for surgery, type and form of transport from Kosovo to

destination center for surgery and still poor technical resources for follow up of this specific

condition.

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036

OUTCOME OF PEDIATRIC PATIENTS WHO UNDERWENT TETRALOGY OF

FALLOT CORRECTION IN CORRELATION WITH THE SURGICAL TECHNIQUE

USED IN RELIEVING THE RVOT OBSTRUCTION L.G. Mandigma, M.B.A. Azcueta, C.A. Estevanez, M.C. Yap

Philippine Heart Center, Quezon City, Philippines

Background and Objectives: Before the advent of surgical intervention, about 50% of patients with

Tetralogy of Fallot died in the first few years of life. In the advent of surgical repair, it has greatly

improved the long-term survival of TOF patients. The objective of this study is to determine the

outcome of pediatric patients who underwent tetralogy of fallot correction in relation to the

surgical technique used in relieving right ventricular outflow tract obstruction (RVOT).

Methods: In this prospective study, 63 patients who underwent tetralogy of fallot correction were

included. Postoperative complications of residual pulmonary stenosis, pulmonary regurgitation,

and right ventricle systolic and diastolic dysfunction were determined and analyzed in correlation

to the surgical technique used to relieve right ventricular outflow tract obstruction.

Results: Residual pulmonary stenosis was observed on all patients for both groups. RV systolic

dysfunction was more common in transannular patching group at 56.5%, compared to pulmonary

valve sparing group at 25%. RV diastolic dysfunction was present in 91.3% of transannular

patching group and 85% in pulmonary valve sparing group. With regards to the distance travelled

in 6 minute walk test, transannular patching group showed a mean of 297 + 71.3m while in

pulmonary valve sparing group, it was 215.3 + 69.2m. 96.7% and 97.5% of transannular patching

group and pulmonary valve sparing group respectively, were in functional class II.

Conclusion: Both RV systolic and diastolic dysfunction are present in the early postoperative

period. Diastolic dysfunction was more common among patients who had transannular patching

while systolic dysfunction was more common among patients who had pulmonary valve sparing.

Pulmonary incompetence was more common among the transannular patching group. Most

patients in both groups were in functional class II and had sub-optimal distance travelled in six

minute walk test.

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SECONDARY PREVENTION, PROGNOSIS, RISK STRATIFICATION, CARDIAC REHABILITATION

037

COMPARISON OF LONG-TERM CLINICAL OUTCOME OF ANGIOTENSIN-

CONVERTING ENZYME INHIBITOR VERSUS ANGIOTENSIN II RECEPTOR

BLOCKER IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

UNDERGOING PERCUTANEOUS CORONARY INTERVENTION H.Y. Kim1, S.M. Lim1, K.Y. Chang1, C.S. Park1, Y.K. Ahn2, M.H. Jeong2, W.S. Chung1,

K.B. Seung1

1. The Catholic University of Korea, Seoul, Korea

2. Chonnam National University, Gwangju, Korea

Angiotensin-converting enzyme inhibitor (ACEi) should be used as the first choice for post

myocardial infarction (MI) and angiotensin II receptor blocker (ARB) should be considered in

patients who are intolerant to ACEi. We consecutively enrolled acute myocardial infarction (AMI)

patients who underwent percutaneous coronary intervention (PCI) from January 2004 to December

2009. Of 4,748 AMI patients, 2,332 and 1,245 patients were treated with ACEi and ARB at

discharge, respectively. The primary endpoint was the incidence rates of all-cause death and

landmark analysis for 1-year post-MI survivors and subgroup analyses were performed. Median

follow-up duration was 43.8 months (interquartile range 29.8 to 60.5 months). In overall

population, long-term survival was superior in ACEi group (201 death, 101.%) as compared with

ARB group (150 death, 15.2%) (p<0.01). In multivariable Cox proportional hazards regression,

adjusted HR is 1.37 (95% CI 1.10 to 1.70, p<0.01). Overall findings were consistent in propensity

matched population. In landmark analysis at 1 year, the incidence rates of all-cause death within 1

year were similar in both groups (adjusted HR 0.90, 95% CI 0.60 to 1.35, p=0.62), whereas,

survival after the first year was superior in ACEi group (adjusted HR 1.83, 95% CI 1.42 to 2.36,

p<0.01). In subgroup analyses, there were significant interaction between preserved (HR 1.07,

95% CI 0.81 to 1.46, p=0.69) and decreased renal function (HR 1.78, 95% CI 1.22 to 2.60, p<0.01,

p for interaction p=0.04) and between STEMI (HR 1.00, 95% CI 0.71 to 1.40) and NSTEMI (HR

1.78, 95% CI 1.26 to 2.50, p<0.01, p for interaction 0.019). Long-term survival of ACEi was

significantly superior than ARB in patients with AMI treated with PCI. ACEi should be remained

as the first-choice of treatment in AMI patients and ARB might be used as alternative with careful

consideration of renal function or clinical diagnosis.

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038

GLOBAL LONGITUDINAL STRAIN AND SEGMENTAL STRAIN PATTERN AS A

PREDICTOR OF OUTCOME IN PATIENTS UNDERGOING AUTOLOGOUS STEM

CELL TRANSPLANTATION FOR MULTIPLE MYELOMA K. Dawson1, J. Minnier2,3, E. Scott3, S. Heitner2

1. Department of Medicine, Oregon Health and Science University, Portland, OR, USA

2. Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA

3. Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA

Introduction: 12-15% of patients diagnosed with multiple myeloma (MM), will develop clinical

amyloidosis (AL) during the course of their disease. The majority of morbidity and mortality of

clinical AL is related to cardiac involvement (CAL). Patients undergoing high-dose myeloablative

chemotherapy are subject to a significant fluid and electrolyte shifts and severe systemic

physiologic stressors. It is not known whether subclinical CAL will affect the outcomes of these

patients. Echocardiography is the imaging modality of choice for the diagnosis of CAL using

calculated global longitudinal strain (GLS) values and segmental longitudinal strain (SLS)

patterns. We hypothesize that using this technique, we would be able to uncover patients with

subclinical cardiac AL, and the values would be a potential predictor for outcomes.

Methods: 115 patients with MM undergoing pre-transplant echocardiography prior to autologous

stem cell transplant (ASCT) were identified from June 2009 to June 2014. The GLS and SLS

patterns were calculated using vendor independent software (EchoInsight®). These were

compared to post-transplant outcomes (30 and 100-day readmission rates, mortality, new

arrhythmia, heart failure, and ischemic events).

Results: Of the 115 patients identified, there were 12 deaths, 33 readmissions, 2 non-ST segment

elevation myocardial infarctions, 11 new arrhythmias, and 10 heart failure episodes. Neither the

GLS value nor SLS pattern provided a sufficiently strong signal for predication of these events in

the patients studied.

Conclusion: In the 115 multiple myeloma patients studied at our institution, neither GLS nor SLS

were able to predict transplant-related mortality or morbidity within the first 100-days. Our study

was subject to the usual limitations of retrospective analyses, as well as the relatively low incidence

of overall events, and the short follow-up. In order to overcome these limitations, and better risk-

stratify patients, larger prospective studies using a combination of imaging and serum biomarkers

is necessary.

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039

LACK OF SOCIAL SUPPORT IS RELATED TO MORE DEPRESSIVE SYMPTOMS

AND WORSE RENAL FUNCTION IN POST-ACS PATIENTS A.L. Arrebola-Moreno1, D. Petrova2, R. Garcia-Retamero3, A. Catena2,

J.A. Ramirez-Hernandez1

1. Virgen de las Nieves University Hospital, Granada, Spain

2. Experimental Psychology Department. University of Granada, Spain

3. Center for Adaptive Behavior and Cognition, Max Plank Institute for Human Development,

Germany

Background and objectives: Both depression and low social support (SS) have been associated

with higher risk of cardiovascular (CV) disease development and mortality. We investigated

potential mechanism though which these psychological factors affect CV prognosis in patients

with acute coronary syndrome (ACS).

Method: Participants were 99 consecutive patients with ACS (mean age=61,SD=9;85%

male).Anthropometric measures and fasting blood samples including levels of blood urea and

creatinine were taken within 3 days after the CV event. Severity of the CV event was measured

with peak levels of myoglobin and troponin, and the severity of the underlying coronary disease

(UCD) with the number of obstructed arteries in the coronary angiography. Participants filled in a

questionnaire including the Beck Depression Inventory and measures of perceived, actual, and

tangible SS.

Results: Twenty-five percent of patients had mild to severe depression. Higher depression scores

were not related to severity of the CV event or the UCD (ps≤.1) but were related to higher levels

of urea(r=.397,p<.001) and creatinine(r=.396,p<.001). Similarly, higher perceived SS was not

related to severity of the CV event or the UCD (ps>.1) but was related to lower levels of

urea(r=−.212,p=.039) and creatinine(r=.−.267,p=.009). Multiple regression analyses controlling

for standard risk factors showed that depression and social support had no independent effects on

renal function. Rather, depression mediated the relationship between SS and renal function.

Conclusions: Although patients who perceived less SS in their lives did not present more severe

CV event or UCV, they reported more depression symptoms shortly after the CV event and had

worse renal function. A possible explanation could be an unhealthier lifestyle, worse hydration or

less drug adherence.

These results suggest that SS has a protective effect on mental health in the face of a serious CV

event and that impaired renal function can be an additional mechanism through which depression

increases CVD recurrence and mortality in patients with ACS.

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LIPIDS, LIPOPROTEIN DISORDERS AND CAD

040

KNOWLEDGE OF CARDIOVASCULAR RISK FACTORS IN HIGH-RISK

POPULATIONS: WHAT PHYSICIANS STAND TO LEARN H.N. Patel, N.T. Aggarwal, A. Volgman

Rush University Medical Center, Chicago, IL, USA

Introduction: Asians in the US are heterogeneous but are grouped together when assessing risk of

cardiovascular disease (CVD). South Asians (SAs) have higher CVD risk. Traditional risk factors

for coronary artery disease (CAD) cannot fully account for increased CAD among SAs. Other

factors, including lipoprotein (a) [Lp(a)], have been identified, and Lp(a) measurements are

important for cardiovascular risk stratification of SAs. We determined physicians’ understanding

of CVD risk among SAs and the likelihood of physicians to pursue risk stratification testing.

Methods: We electronically surveyed 100 Internal Medicine and Cardiology physicians on CVD

risk among SAs and on CVD testing.

Results: Among responders, 38% identified SAs as the ethnic group with the highest CAD risk,

and 71% were “very likely” to order lipid testing in patients with a strong family history (FH) of

CAD, but only 43% knew which type of advanced lipid testing to order. Physicians acknowledged

FH was the strongest predictor of CAD in SAs (40%), followed by Lp(a) (28%) and elevated total

cholesterol-to-HDL ratio (17%). Forty percent would not order genetic testing in patients with a

strong FH of CAD; 88% did not know which genetic tests to order.

Conclusion: Despite strong data, most physicians are unaware of the high risk of CAD in SA and

are unaware of how to pursue advanced lipid and genetic testing in high risk populations. In

addition, physicians may be unaware of the risk stratification tools available and when to utilize

these tests. Education and increased awareness regarding the increased risk of CVD in the SA

population among physicians may decrease the high mortality and morbidity rates observed in this

ethnic group.

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041

THE STATIN MYALGIA CLINICAL INDEX (SMCI): ENHANCEMENTS AFTER

COGNITIVE INTERVIEWS WITH PHYSICIANS

K. Miller1, M. Bayliss1, D. Chibedi De-Roche2, M. Baccara-Dinet2, I. Khan4, M. White1,

R. Sanchez5 1. Optum, Lincoln, RI, USA

2. Sanofi Paris, France

3. Sanofi, Montpellier, France

4. Sanofi, Bridgewater, NJ, USA

5. Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA

Background: Patients who experience muscle symptoms while taking statins often become non-

adherent. However, attributing symptoms to statin use is clinically difficult. The new Statin

Myalgia Clinical Index (SMCI), proposed by the National Lipid Association and included in a

consensus statement of the European Atherosclerosis Society, evaluates the likelihood that statins

caused a patient’s muscle complaints rather than some other cause. We sought to revise the SMCI

and prepare it for use in clinical practice.

Methods: The SMCI was revised based on structured qualitative interviews with three of the

authors of the original publication and cognitive debriefing interviews with ten physicians (six

cardiologists, two lipidologists, and two primary care physicians). To maximize the clarity of the

SMCI, we applied rigorous methods recommended by the FDA and EMA for clinical outcome

assessment development.

Results: Based on recommendations from the qualitative interviews, the revised SMCI includes

new instructions and formatting to aid understanding, completion, and scoring. One instruction on

distinguishing between two statin challenges was unclear to most clinicians; we significantly

revised the layout and visual appearance of the SMCI in response. Where appropriate, clinicians’

minor suggestions regarding language were implemented. Otherwise, clinicians generally found

the SMCI items, response choices, scoring and interpretation clear and understandable.

Conclusions: The SMCI assesses the likelihood that muscle symptoms are due to statin use. In

preparation for testing the SMCI in clinical practice, this study refined the SMCI based on

cognitive interviews with clinicians. Tests of clinical application and inter-rater reliability are

underway.

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042

HYPERURICEMIA IS ASSOCIATED WITH WORSE LIPIDS PROFILE AND

CARDIAC FUNCTION IN ELDERLY ATRIAL FIBRILLATION PATIENTS W.Y. Liang, M.L. Liu, W. Xiang, J.W. Zhang, X.R. Feng

Peking University First Hospital, Beijing, China

Objectives: To investigate factors associated with hyperuricemia in elderly patients with non-

valvular atrial fibrillation (AF).

Background: AF and hyperuricemia are common diseases in elderly. Accumulated evidences

indicate that hyperuricemia is a possible risk factor of cardiovascular diseases.

Methods: Consecutive elderly patients (over age 60) with non-valvular AF were retrospectively

recruited in this study from the inpatient clinic between January 2012 and December 2013. We

excluded subjects with cardiomyopathy, severe hepatic or renal dysfunction, thyroid dysfunction,

chronic anemia, active inflammatory conditions, autoimmune diseases, and those who were taking

uric acid-lowering drugs. The final study population included 611 patients (363 men and 248

women). Hyperuricemia was defined as serum uric acid (SUA) concentration > 7 mg/dL.

Results: The prevalence of hyperuricemia was 22.7% in the non-valvular AF population, 69.1%

and 30.9% in men and women, respectively. Body mass index was significantly higher in

hyperuricemia group than SUA normal group (p < 0.001). Consistently with elevated SUA, higher

levels of serum creatinine, blood urea nitrogen and lower estimated glomerular filtration rate were

found in hyperuricemia group (all p values < 0.001). Patients with hyperuricemia also had higher

level of triglyceride and lower level of HDL than those in the SUA normal group (p < 0.001),

indicating a worse lipids profile in hyperuricemia group. Besides, levels of B-type natriuretic

peptide, left atrial diameter, LV mass index and percentage of NYHA class III/IV were

significantly higher in hyperuricemia group than SUA normal group, indicating worse cardiac

function (all p values <0.01). Treatment with diuretics and angiotensin-converting enzyme

inhibitors were more prevalent in hyperuricemia group (p < 0.001).

Conclusions: Among elderly non-valvular AF population, elevated SUA was combined with

poorer renal function. Worse lipids profile and cardiac function existed in patients with

hyperuricemia.

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PREDICTORS AND MARKERS OF HEART FAILURE OUTCOME

043

LEFT ATRIAL ENLARGEMENT AS A MARKER OF SEVERITY OF DIASTOLIC

DYSFUNCTION AND CORRELATION WITH DEMOGRAPHICS P. Rodriguez-Lozano, S. Raslan, A. Melhem, M. Shea, A. Khan, P. Nalabothu,

M. Morsy, W.I. Khalife

UTMB, Galveston, TX, USA

Objective: To determine the prevalence of left atrial (LA) enlargement and its relation to left

ventricular (LV) diastolic dysfunction.

Methods: We retrospectively reviewed 2,265 medical records of patients receiving

Echocardiograms at a University hospital between 2008 year and 2012 year. The patients were

divided into four groups according to level of diastolic dysfunction. LV diastolic function was

evaluated by measuring the peak velocity of early (E) and late (A) diastolic transmitral blood flow,

peak early diastolic mitral annular velocity (E') by Tissue Doppler echocardiography, and

pulmonary venous sampling.

Results: In this study, correlations between LA index and echocardiographic features of left

ventricular (LV) diastolic function. Bivariate analyses showed higher mean LA index values in

patients with Pseudonormal and Restrictive DD compared with controls and in patients with

impaired relaxation ( 22.7, std. dev.9.4, 22.6, std.dev. 9.9, 29.5 std. dev 13.8, and 33.0, std.dev.

11.3, p<0.0001).In the logistic regression model with LA index, BMI and Age as predictor

variables for the outcome of DDX severity, both LA index and Age were statistically significantly

associated with DDX severity (LA index: OR=1.022, 95% CI=1.010-1.034, p=0.0004; Age:

OR=1.051, 95% CI=1.041-1.060, p<0.0001). In the model with LA volume, BMI and Age, both

LA volume and Age were statistically significantly associated with DDX severity (LA vol:

OR=1.010, 95% CI=1.004-1.017, p=0.0009; Age: OR=1.051, 95% CI=1.042-1.060, p<0.0001).

Conclusions: LA Index and LA volume were higher in patients with Pseudonormal and Restrictive

Diastolic Dysfunction than in control. Age was an independent predictor for DD. BMI was an

independent predictor for DD.

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PREDICTORS AND MARKERS OF HEART FAILURE OUTCOME

044

LEFT ATRIAL ENLARGEMENT IN PATIENTS WITH ATRIAL FIBRILLATION AND

STROKE AND DIASTOLIC DYSFUNCTION P. Rodriguez-Lozano, S. Raslan, A. Melhem, M. Shea, A. Khan, P. Nalabothu,

M. Morsy, W.I. Khalife, M. Alghrouz


Background: Whether LA enlargement is a predictor for atrial fibrillation and stroke in patients

with DD is unknown.

Objective: We conducted an analysis to investigate the association.

Methods: We retrospectively analyzed echocardiograms of 1568 patients performed at University

hospital. 154 with atrial fibrillation, & 157 with stroke. For this analysis, there were 717 patients

with complete data.

Results: In the logistic regression analysis we found that LA Index/LA volume was a predictor

marker for development of Atrial fibrillation in patients adjusting for DD (LA volume: OR=1.021,

95% CI=1.010-1.032, p=0.0002). The model with LA index yielded similar results (OR=1.044,

95% CI=1.020-1.068, p=0.0002). Furthermore, we examined the outcome of stroke with the

predictor variables AF, DD, and LA volume. Neither LA volume (p=0.3397) nor LA index

(p=0.3390) were associated with Stroke in patients in models adjusting for DD and Atrial

fibrillation (p=0.4834). DD was the only covariate found to be significantly associated with stroke

(OR=1.911, 95%CI=1.031-3.539, p=0.0395).

Conclusion: Increased LA volume and LA index are both significant predictors of AF in patients

adjusting for DD. No association between either LA volume or LA index was found with stroke

as the outcome.

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PULMONARY CIRCULATION ASPECTS, PULMONARY HYPERTENSION

045

PROGNOSTIC VALUE OF RIGHT ATRIAL FUNCTION AND DIMENSION IN

PATIENTS WITH PULMONARY HYPERTENSION R. Placido, N. Cortez-Dias, S.R. Martins, T. Guimaraes, S. Goncalves, L. Santos,

E. Infante de Oliveira, A.G. Almeida, F. Pinto

Hospital Santa Maria, Serv Cardiologia I, Lisbon Academic Medical Centre, CCUL, Lisbon,

Portugal

Introduction: Clinical assessment is essential when evaluating patients with suspected pulmonar

hypertension (PH), however, echocardiography is a key screening tool in the diagnostic algorithm.

Right ventricular dysfunction has been associated with adverse outcomes but few studies have

focused on the structure and function of the right atrium (RA).Objectives: To determine the

prognostic value of RA dimensional and functional parameters in patients with PH.

Methods: Prospective study of patients with PH undergoing clinical and echocardiographic

evaluation, focusing on RA dimensions and deformation analysis. Association with the composite

endpoint death or hospitalization for cardiac causes was tested using the Kaplan-Meier analysis

and Cox multivariate regression analysis. The prognostic accuracy was evaluated by the area under

the receiver operator curve.

Results: Seventy-seven patients (75% female; 55 ± 16 years; 68% with group 1 PH) were included.

At baseline atrial dimensions were: diastolic area - 24.4±13.1 cm2; systolic area - 19.3±11.1 cm2;

longitudinal diameter 4C view - 56.9±12.9 mm. During a median follow-up of 25 months, 9

patients died and 29 were hospitalized for cardiac causes. The composite endpoint occurred in

39% (N = 30) and the risk increased with the RA size and reduction of atrial systolic deformation.

The risk of events increased 6% per cm2 of increased area (HR: 1.06; 95% CI 1.03-1.10; p=0.001).

Longitudinal systolic strain of all septal segments and lateroapical segment were strong prognostic

predictors. The risk of events increased 7% for each 1% of deformation reduction (HR: 1.07; 95%

CI 1,02-1.13; P=0.003). Midseptal segment longitudinal systolic strain was the strongest

prognostic predictor by multivariate Cox regression analysis (including all RA echocardiographic

parameters) (HR: 1.10; 95% CI 1.02 to 1 18; P = 0.012).

Conclusions: RA function and dimension showed prognostic value in PH and should be considered

in the echocardiographic assessment of these patients.

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046

DETERMINANTS OF SUBCLINICAL ATHEROSCLEROSIS IN PATIENTS WITH

OBSTRUCTIVE SLEEP APNEA I. Tomeckova1,2, M. Kozarova2,3, D. Petrasova4, I. Paranicova1,2, Z. Malachovska2,3,

I. Tkac2,3, P. Joppa1,2, R. Tkacova1,2

1. Department of Respiratory Medicine, Safarik University, Medical Faculty, Kosice, Slovakia

2. L. Pasteur University Hospital, Kosice, Slovakia

3. Department of Medicine, Safarik University, Medical Faculty, Kosice, Slovakia

4. Laboratory of Research Biomodels, Safarik University, Medical Faculty, Kosice, Slovakia

Background: Patients with obstructive sleep apnea (OSA) have increased cardiovascular risk. In

these patients, intermittent hypoxia increases sympathetic activity, systemic inflammation and

oxidative stress which may all contribute to accelerated atherosclerosis. Our aim was to investigate

relationships between carotid intima-media thickness (IMT) and OSA severity, markers of

oxidative stress and systemic inflammation.

Methods: 84 subjects [mean age (mean±SD) 47.1±9.7 years, body mass index (BMI) 30.1±4.1

kg/m2] underwent overnight polysomnography (Alice 4, Respironics, Murrysville, USA).

Subjects were divided into three groups: no OSA [apnea-hypopnea index (AHI) 3.2±1.1

events/hour]; mild-moderate OSA (AHI 15.8±6.7 events/hour), and severe OSA (AHI 48.3±16.0

events/hour). Carotid intima-media thickness (IMT) was assessed by B-mode ultrasound (Philips

HD11 XE), arterial pulse wave velocity (PWV) was measured using the automatic Complior

device.

Results: Both IMT and PWV increased from subjects with no OSA to patients with mild-moderate,

and to those with severe OSA (0.54±0.10 vs 0.59±0.07 vs 0.62±0.11 mm, p=0.037; 8.9±1.0 vs

10.3±1.3 vs 9.8±1.6 m/s, p=0.026, respectively). In addition, circulating oxidized LDL (oxLDL)

and lipopolysacharid levels increased with OSA severity (p=0.007, p=0.046, respectively). In

multivariate models, age (p<0.001), oxygen desaturation index (p=0.031) and oxLDL (p=0.005,

r2=0.329) predicted IMT independently of gender and BMI.

Conclusions: In patients with OSA, older age, nocturnal intermittent hypoxia reflecting OSA

severity and oxLDL were independent correlates of ultrasonographic carotid atherosclerosis.

Support: APVV-0134-11, Ministry of Education, Slovakia

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047

ROLE OF THE ELECTROCARDIOGRAPHY FOR EARLY RISK STRATIFICATION

IN ACUTE PULMONARY EMBOLISM D.B. Petrov, M.H. Milanova

Emergency Hospital "Pirogov" Sofia, Bulgaria

Objective: We investigated 12-lead electrocardiographic (ECG) patterns in acute pulmonary

embolism (PE) to evaluate the role of the ECG score in risk stratification of patients with acute

PE.

Background: Date on the usefulness of combination of different ECG abnormalities in risk

stratification of patients with acute PE are limited.

Methods: Our study enrolled one hundred thirty four(134) consecutive patients admitted in

Emergency Hospital "Pirogov" with the diagnosis of acute PE(confirmed by spiral computed

tomography scan) from June 2007 to December 2014.We analyzed ECG patterns and calculated

the ECG score in all patients. The ECGs were recorded at standard gain (10mV/mm) and speed

(25mm/s).We evaluated right ventricular systolic pressure (RVSP) (n=76) and right

ventricular(RV) hypokinesia (n=87) using echocardiography for risk stratification of acute PE

patients. Subjects with undeterminet onset of PE or without available ECGs were excluded from

the present study. Given the fact, that echocardiography may be of poor quality in overweight and

mechanically ventilated patients, or in those with chronic pulmonary disease, these groups of

patients were also excluded from the study.

Results: Among several ECG findings sinus tachycardia (90%), right axis deviation (76%),

inverted T waves in leads V1-V4 (65%) and right bundle branch block (40%) were observed most

frequently. The mean ECG score and RVSP were 7.38 ±6.32 and 53 ±20 mmHg respectively. The

ECG score correlated with RVSP(r=0.266, p=0.015).The patients were divided into two groups:

high ECG score group (n=98) with ECG score>12, and low ECG score group (n=36) with

score<12, based on the ECG score with the maximum area under the curve. RV hypokinesia was

observed more frequently in the high ECG score group, than in the low ECG score group

(p=0.006). Multyvariate analysis revealed that a high ECG score was an independent predictor of

high RVSP and hypokinesia.

Conclusions: ECG may be a useful, simple, non-costly tool for initial risk stratification of patients

with acute PE in the Emergency Departments and for guiding further diagnostic work-up

decisions. Using the ECG for management warrants prospective evaluation.

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048

PULMONARY HYPERTENSION IN A PATIENT WITH CONGENITAL HEART

DEFECTS AND HETEROTAXY SYNDROME H. Keshmiri1, T. Yousuf1, J. Kramer2

1. Advocate Christ Medical Center, Chicago, IL, USA

2. Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA

Background: Heterotaxy syndrome is a rare clinical entity characterized by presence of abnormal

position of the viscera, congenital heart defects and splenic malformations. There have been very

few reported cases of heterotaxy syndrome that manifest with pulmonary hypertension in

adulthood.

Case: 26 year old male with history of heterotaxy syndrome diagnosed as a fetus with multiple

cardiovascular surgeries presented to the hospital with shortness of breath. Anatomical

abnormalities related to heterotaxy syndrome in our patient included double outlet right ventricle

with complete AV septal defect (Rastelli type A), asplenia, pulmonary atresia, interrupted inferior

vena cava with azygous continuation to the right superior vena cava and total anomalous

pulmonary venous return to the innominate vein. Echocardiogram was done during the hospital

course that revealed elevated pulmonary artery pressure. The pulmonary pressures obtained

through right heart catheterization six months prior were normal. To confirm the diagnosis of

pulmonary hypertension, right heart catheterization was repeated which revealed elevated

pulmonary artery pressure at 71/38 mm Hg with mean of 51 mm Hg and elevated pulmonary

vascular resistance (PVR) of 4.9 Wood Units. Pulmonary capillary wedge pressure was within

normal range. Vasoreactivity test was negative. Patient was started on bosentan for management

of pulmonary hypertension.

Conclusion: There has been one previously reported case of pulmonary hypertension in an adult

with heterotaxy syndrome in a structurally and functionally normal heart. To the best of our

knowledge, pulmonary hypertension has not been previously described as the prominent clinical

feature of patients with heterotaxy syndrome with congenital heart disease. Development of

pulmonary hypertension may be secondary to congenital heart defects resulting in left-right blood

shunting, vascular malformations leading to portopulmonary shunts or non-cardiac malformations

such as asplenia.

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049

MASSIVE PULMONARY EMBOLI FOLLOWING DISCONTINUATION OF

RIVAROXABAN P. Samani, J. Bohinc, M. Quraishi, H. Hahn, B. Schwartz

Kettering Medical Center, Kettering, Ohio, USA

Introduction: The use of novel oral anticoagulants (NOACs) for stroke and systemic embolism

prevention in non-valvular atrial fibrillation and as treatment of pulmonary and systemic venous

thromboembolism (VTE) has become increasingly common. To date, data regarding patient

outcomes following discontinuation has not been well studied. We present a patient who developed

massive bilateral pulmonary emboli (PE) following discontinuation of rivaroxaban.

Case Study: A 69 year old male initially presented to our facility with a right thalamic intracranial

hemorrhage. The patient was chronically on rivaroxaban for paroxysmal atrial fibrillation, which

was discontinued on admission. Two days later he developed shortness of breath. A Computed

tomography angiogram revealed multiple bilateral PE. Ultrasound of the lower extremities did not

reveal deep vein thrombosis (DVT). An inferior vena cava filter was placed. The patient was

discharged to inpatient rehab. On hospital day 32, the patient developed acute respiratory failure.

Echocardiography revealed a severely dilated right ventricle. The patient went for emergent

pulmonary embolectomy at which time massive bilateral thrombosis was noted. Ultrasound of the

lower extremities revealed bilateral acute and subacute DVT.

Discussion: Our patient presented with massive bilateral PE after discontinuation of rivaroxaban

following an acute intracranial bleed. To our knowledge, this is the first case of post marketing

massive pulmonary emboli following discontinuation of rivaroxaban. Workup revealed no other

obvious cause for hypercoagulable state . This case brings to light the potential complications with

discontinuation of NOAC therapy. Whether or not NOACs promote a hypercoagulable state

remains unclear and deserves further investigation.

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050

NOVEL ECG PREDICTORS FOR PULMONARY EMBOLISM H.H Mehta, A. Vishnevsky, J. Finkel, N. Fonseka, G. Marhefka

Thomas Jefferson University Hospital, Philadelphia, PA, USA

Background: Acute pulmonary embolism (PE) is a common and highly morbid disease with a

mortality rate approaching 30 percent if left untreated. Presenting symptoms can mimic acute

coronary syndrome. Though CT angiography (CTA) is gold standard for diagnosis, it carries risk

for contrast induced adverse effects and radiation exposure. Electrocardiogram (ECG) is an

inexpensive tool that can aid in diagnosis of PE, and help expedite therapy. However, current data

is based mostly on small retrospective studies.

Methods: We identified 300 patients diagnosed with acute PE by CTA, and retrospectively

gathered data including patient characteristics, type of PE, its hemodynamic significance and

associated ECG findings in hopes of discerning which of the previously associated ECG changes

had an acceptable diagnostic sensitivity for acute PE.

Results: We found that ECG changes, including classic ones like sinus tachycardia (25%; CI 19.5

to 30.3) and S1Q3T3 (11%; CI 7.1 to 15.0), had very limited sensitivity in our patient sample. The

most common ECG changes in our cohort included 1. T wave inversion in leads III and a VF (43%;

CI 36.6 to 49.1), 2. T wave inversion in any 2 contiguous leads (53%; CI 46.8 to 59.3), 3. Atrial

arrhythmias of any type (39%; CI 33.0 to 45.3), and 4. Slurred S waves in leads V1 and/ or V4

(38%, CI 32.2 to 44.5). Significantly, the associations became stronger as the size of the PE

increased. Furthermore, saddle PE was significantly associated with a tall R wave >1.5mm in lead

aVR (40%; CI 0.05 to 0.75).

Conclusion: By using the largest cohort of patients ever examined for ECG changes in acute PE,

we showed that classic markers have limited utility in PE diagnosis. We propose novel ECG

markers that have stronger predictive value for PE, and, when present, can also be suggestive of

PE size.

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CARDIOVASCULAR ASPECTS IN RENAL DISEASE

051

ASSOCIATION OF CORONARY ARTERY CALCIFICATION AND ARTERIAL

MICRO-CALCIFICATION OF THE VASCULAR ACCESS IN INCIDENT

HEMODIALYSIS PATIENTS

Y.O. Kim, S.J. Choi, B.S. Kim, H.C. Song

Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul,

Korea

Background: We have reported that arterial micro-calcification (AMC) of vascular access has a

negative impact on access patency and cardiovascular mortality in hemodialysis (HD) patients.

Reasons behind increased cardiovascular mortality in AMC are not fully understood, but it is

believed that aortic stiffness is a major contributing factor. Whereas, coronary artery calcification

(CAC) is quite common in HD patients and it is known as predictor of future cardiovascular events

and all-cause mortality in HD patients. The aim of this study was to explore the relationship

between AMC and CAC in HD patients.

Methods: 95 HD patients who received vascular access operation were included in this study. The

AMC was diagnosed by pathologic examination of arterial specimen by von Kossa stain, which

was acquired during the operation. All patients underwent a multi-detector computed tomography

(MDCT) imaging procedure and coronary artery calcium score (CACS) was calculated. Patients

were classified into two groups, according to the CACS, as high (>100), in 56 patients, and low

(<100), in 39 patients. We compared AMC and several parameters between the patients with high

and low CACS groups.

Results: Mean age was 65.4 +/- 12.7 years and the male gender was 63.2% (n=60). The incidence

of AMC was 55.8% (n=53). The mean CACS was 456.7 +/- 697.2 and distributed from zero to

3880. Patients with high CACS group were older (69.6 +/- 9.5 vs. 59.4 +/- 14.1, p=0.007), and

showed a significantly higher prevalence of diabetes mellitus (75.0% vs. 53.8%, p=0.027). High

CACS group showed high incidence of AMC compared to low CACS group (71.4% vs. 33.3%,

p<0.001). By binary logistic regression, AMC was independently associated with high CACS (OR:

4.228, 95% confidence interval [CI]: 1.513-11.817, p = 0.006).

Conclusion: The present study suggests that AMC is closely associated with CAC in incident HD

patients.

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CARDIOVASCULAR ASPECTS IN RENAL DISEASE

052

INCREASE OF SEMAPHORIN 3C EXPRESSION IN POLYCYSTIC KIDNEY

ACCOMPANIED BY ENDOTHELIAL-TO-MESENCHYMAL TRANSITION B.H. Kim, J.Y. Ko, D.Y. Kim, J.H. Park

The Department of Biological Science, Sookmyung Women's University, Seoul,

South Korea

EndMT is a phenomenon that an endothelial cell loses its characteristic and acquires mesenchymal

cell specific feature. It is known to be crucial for heart development. However, as it was found that

EndMT was involved in the cardiac fibrosis, pathological effect of EndMT has not been identified

in other organs. Polycystic kidney disease (PKD) is a genetic disease and accompanied by EndMT.

However, regulatory mechanism between EndMT and PKD progression is not clear. In this study,

we focused on Semaphorin 3C to elucidate mechanism of PKD development derived by EndMT.

Specific markers for EndMT were quantified in various PKD mouse models. Also, expression of

Semaphorin 3C level was validated in PKD mouse models and PKD patient. To confirm the effect

of Semaphorin 3C on EndMT and polycystic kidney, specific disease markers were evaluated in

Semaphorin 3C KD or OE cells. As a result, markers for EndMT were significantly changed in

experimental mouse compared to control. Also, it was found that Semaphorin 3C expression was

correlated to EndMT and PKD progression. In conclusion, we suggest that EndMT is the one of

contributors to PKD progression, which is associated with dysregulated expression of Semaphorin

3C.

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CARDIOVASCULAR QUALITY IMPROVEMENT AND OUTCOME

053

OBSERVATION UNIT CARE: A COMPARISON OF SPECIALIZED CARDIAC

VERSES GENERALIZED OU DESIGN D.N. Hurley1, D. Stansky2, J.W. Huppertz2, D.P. McKenna1, M.S. Sidhu1

1. Albany Medical College, Albany, NY, USA

2. Union Graduate College, Schenectady, NY, USA

Given the escalating costs of medical care in the United States hospitals have faced significant

pressure to reduce costs, particularly from unnecessary admissions and readmission of patients.

One approach suggested to improve quality of care and reduce cost burden has been the

Observation Unit (OU). The impact of OU care on specific patient groups, however, is a field not

well studied. Our study aims to compare the resource utilization of a specialized Cardiac Care OU

with a general medical OU. We reviewed charts for 83 patients in the CCOU and 295 GMOU at

our tertiary care academic center (55% female, average age 56). Data was retrospectively collected

on floor time, time of discharge, consults ordered, imaging studies, EKGs, and labs ordered. Mean

total floor time was found to differ between the two groups, with CCOU averaging 34 hours and

GMOU averaging 41 hours (p=.019). No difference was found in the discharge delay, or the time

from discharge order to patient discharge (2.5hrs vs 2.7hrs for GMOU OU, p=.56). CCOU patients

received more EKGs than GMOU patients (1.8 vs 1, p<.001). However, there was no difference

in total resource utilization (labs, imaging studies, or consults ordered) between the two groups (8

vs 8.3, 1.5 vs 1.4, .6 vs .5, p>.05). Interestingly, 23% of CCOU patients and 28% of GMOU

patients had no procedures, labs, or imaging studies conducted during the 12 hour overnight period

prior to discharge. This could suggest that patients are unnecessarily waiting for a discharge order

while medically ready for discharge. Additionally, shorter mean total floor time with equal

resource utilization suggests that the specialized CCOU was more efficient at providing the same

quantitative level of care. Further research into the impacts of specialized OU care is warranted to

improve patient outcomes.

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054

NEGLECTED GUIDELINES OF STAPHYLOCOCCUS AUREUS BACTEREMIA A. Dutta, J. Goldman, P. Cheriyath, Y. Wert

Pinnacle Health (Harrisburg Hospital), Harrisburg, PA, USA

Introduction: Staphylococcus aureus is a leading cause of both community-acquired and

healthcare-acquired bacteremia resulting in mortality. There are increasing concerns in health care

community regarding the physician’s compliance with recommended guidelines. Literature has

suggested that with bundle management, there has been documented improved morbidity and

mortality. Our study reveals increased mortality in patients diagnosed with staphylococcus aureus

bacteremia and infective endocarditis.

Hypothesis: Staphylococcus aureus bacteremia predisposes patients to endocarditis, not following

recommended guidelines predisposes to mortality and complications.

Methods: Retrospective chart review of hospital patients admitted from January 2011 to

December 31 2012. Covariables which predisposed to infection were documented: age, sex,

history of bacteremia or endocarditis, IV drug abuse, line infections, and an immunocompromised

state. Our analysis consisted of 200 patients with primary outcome of endocarditis and secondary

outcomes of use of repeat blood cultures, transthoracic echocardiograms, transesophageal

echocardiograms, and infectious disease consults.

Results: 152/200 (76%) patients had repeat blood cultures, 122/200 (61%) patients received

transthoracic echocardiograms, 48/200 (24%) patients received transesophageal echocardiograms,

and 153/200 (76.5%) patients had infectious disease consults. Out of the 200 patients with MRSA

bacteremia, 20/200 (10%) were diagnosed with endocarditis, 5/20 patients with endocarditis died

revealing a 25% mortality rate. Overall, 24% of patients did not receive repeat blood cultures, 24%

patients did not receive infectious disease consults, and 33% patients did not receive imaging

(TTE/TEE). The national mortality of endocarditis is 18%, our hospital system revealed 25%

mortality.

Conclusion: According to the IDSA guidelines of staphylococcus aureus bacteremia, transthoracic

echocardiography is a class I A recommendation in all suspected cases of infective endocarditis.

We recommend imaging in all suspected cases of infective endocarditis, involving infectious

disease specialists, and repeating blood cultures to document clearance of infection. We hope that

applying these guidelines, there is an opportunity to decrease mortality.

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055

DIAGNOSTIC YIELD AND INFLUENCE ON MANAGEMENT OF

ECHOCARDIOGRAPHY PERFORMED FOR EVALUATION OF SYNCOPE D.N. Hurley, M.S. Sidhu, M.T. Torosoff

Albany Medical College, Albany, NY, USA.

We investigated the utility of an echocardiogram performed on arrival in patients presenting to the

ED with syncope and whether results would affect subsequent acute in hospital clinical

management. Our study included 200 consecutive patients with transthoracic echocardiogram

performed for evaluation of syncope. The study cohort consisted of 50% females, 38% current

smokers, 60% with history of hypertension, 32% with CAD and 8% with prior MI, 6% with chest

pain on admission, 22% with diabetes, 8% with history of heart failure, and 9% with prior CVA.

All echocardiograms were performed at a single academic medical center for the primary

indication of syncope. Echocardiographic findings changed the diagnosis and affected the

management in 10.6% of cases. Discharge following the echocardiogram was twice as likely if the

echocardiogram was unrevealing (35% vs. 16%, p=0.095). Bradycardia, complete heart block, or

atrial fibrillation was noted in 36% of cases. Subsequent arrhythmias during hospital stay led to

diagnosis change in 16 patients and of these, the echocardiogram was unrevealing in 75% of cases.

Echocardiographic findings associated with change in management included cardiomyopathy

(n=8), pulmonary hypertension (n=8), inter-atrial shunting (n=4), and RV dysfunction (n=4).

Change in management was more likely in males (16% vs. 4% in females, p=0.008) and in patients

with chest pain (16% vs 5%, p=0.06). The change was less likely in patients with history of CAD

(5% vs. 13%, p=0.112) or CVA (0% vs. 11%, p=0.149). Thus, echocardiographic yield in the

evaluation of syncope is modest and is significantly influenced by associated co-morbidities,

arguing against protocol-driven routine use of echocardiography in all syncope patients. More

studies of this important subject are warranted to better understand the role of echocardiography

in the evaluation of syncope.

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056

THE ECHOCARDIOGRAPHY APPROPRIATENESS USE CRITERIA PARADOX:

MORE STUDIES FOR APPROPRIATE REASONS? K.W. Wong1, D.F. Distel3, V. Kumar1, N. Yager1, M.S. Sidhu1,2, D.P. McKenna1,

M.T. Torosoff1, S.A. Fein1

1. Albany Medical Center, Albany, NY, USA

2. Stratton VA Medical Center, Albany, NY, USA


Background: The use of inpatient echocardiography has increased dramatically in recent years.

The impact of this increase in volume on the adherence to the echocardiography appropriate use

criteria has not been well studied.

Material and Methods: Our pilot study involved a review of 529 medical charts and consecutive

inpatient transthoracic echocardiograms performed at a single medium-sized academic medical

center for the indications of coronary artery disease (CAD), congestive heart failure (CHF), and

infective endocarditis (IE) to determine appropriateness based on 2011 appropriate use criteria

(AUC).

Results: We have observed a significant rise in utilization of echocardiography for these

indications. For congestive heart failure alone, there was an increase of 142% in February 2014

and 495% in July 2014 compared to the same months in 2010. Of 529 echocardiograms, 126

(23.8%) were for CHF, 23 (4.3%) for IE, 26 (4.9%) for CAD. A sample of 80 consecutive

echocardiograms was reviewed and scored for appropriateness: 23 (29%) CHF, 28 (35%) CAD,

and 10 (13%) IE. Nineteen (24%) cases were not scored due to limited information in the EMR.

Overall, 58 (95%) cases were deemed appropriate.

Conclusions: Despite the dramatic increase in the utilization of echocardiography in recent years,

for CHF, CAD, and IE, the vast majority of studies met appropriateness use criteria. Wider

dissemination of AUC criteria may actually lead to a large number of appropriately ordered tests.

Additional studies of this important subject are required.

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057

HEART FAILURE SUPPORTIVE CARE CLINIC: DOES IT IMPROVE QUALITY OF

LIFE? F. Simpson1, T. Hahn1, C. Nordquist1, A. Kaan1, D. Ross2, L. Leung1, A. Ignaszewski1,3,

G. Kimel1,3

1. Providence Health Care, Vancouver, BC, Canada

2. Vancouver Coastal Health, Vancouver, BC, Canada

3. University of British Columbia, Vancouver, BC, Canada

Objectives: To evaluate the Heart Failure Supportive Care (HeF) Clinic at St. Paul’s Hospital in

Vancouver, BC. The goal of the clinic, which opened in January 2011, is to assess and treat patients

with advanced heart failure (HF) who have severe symptoms despite maximal medical therapy.

We hypothesized that early referral to the HeF Clinic would improve quality of live (QOL) and

decrease hospital admissions for decompensated HF.

Background: Heart disease is one of the leading causes of death in Canada and is associated with

high morbidity and mortality, a negative impact on QOL, and high health care costs. However, too

few patients with advanced HF are offered appropriate palliative care and few resources are

directed to the palliative needs of those patients.

Methods: We conducted an observational descriptive study to validate the suggested clinical

benefit of the HeF Clinic. Data was collected from the clinical reports of the clinic’s patients.

Outcome measures included Edmonton Symptom Assessment System (ESAS) scores and number

of hospital admissions for HF.

Results and Conclusions: Approximately 75% of patients were NYHA Class III or IV. Patients’

QOL as measured by ESAS was improved or stabilized in most patients (67% of patients had

improved ESAS scores and another 11% had stable scores). Furthermore, of the 28 most recent

patients, only 7 were admitted to hospital for decompensated HF. Most patients with HF can be

effectively managed by their family physician, however, patients with severe symptoms and

multiple co-morbidities may benefit from early referral to this clinic.

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COMPUTERS IN CARDIOLOGY

058

NOVEL SIMULATION-BASED TRAINING IN CARDIOLOGY: TRAINEE FEEDBACK

AND EVALUATION OF A PILOT STUDY C. Costopoulos, T. Kelay, E. Ako, M. Yasin, K.L. Chan, M. Gold, R. Kneebone, F. Bello,

I.S. Malik

Imperial College London, UK

Background: Simulation is used to enhance safety in non-medical and medical professions. Our

unit has previously validated carotid simulation training. This paper presents initial trainee

feedback for a novel course for cardiology.

Methods: Participants 33 cardiology trainees were recruited, from ST3 to advanced training levels.

Training Facility & Simulator Device: 7 pilot cases utilized the Imperial Distributed Simulation

Concept. 26 sessions used the ORCamp suite (ORZone), comprising an integrated VR simulator

(Mentice VIST®-C), simulated patient (trained actor) and multidisciplinary team.

Testing Format: Scenarios were allocated from a portfolio of 16 cases, commencing with case

history, leading on to decision-making (e.g. type of procedure, tool selection), proceeding on to

simulated complications/crises.

Evaluation Techniques: Participants rated the realism of the simulator and evaluated the training

experience, including potential for implementation.

Statistical Analysis: Quantitative data was analysed using the Statistical Package for the Social

Sciences (SPSS), Version 22.0.

Results: Demographics Twelve ST3’s, eight ST4’a, six ST5’s, five ST6, two interventional

fellows.

Evaluation & Feedback

1. Realism of Simulator

Participants agreed that the simulated model is realistic (mean = 4.68, std. dev = 0.476 and useful

for training interventionalists (mean = 4.76, std. dev = 0.523).

2. Evaluation of the Training Environment & Experience

Participants rated the experience positively in terms of replicating the workplace and pathway, for

team training and as a format to assess workplace performance.

3. Potential for Training Implementation

Simulation was deemed most useful for crisis training and transfer to clinical practice.

Conclusion: Simulation training can be a helpful learning tool for cardiology trainees, successfully

replicating serious and life-threatening scenarios encountered in the catheterization laboratory.

This has the potential of improving patient safety by providing trainees with the necessary skills

to manage such cases prior to hands-on experience with real patients.

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059

IPHONE ACQUIRED HEART RHYTHM: IS IT RELIABLE FOR CLINICAL

DIAGNOSIS?

O.S. Sandhu

California Heart Medical Associates, Fresno, CA, USA

The purpose of this study was to validate the reliable use of an iPhone acquired heart rhythm for

clinical diagnosis of cardiac arrhythmias to help make early diagnosis of cardiovascular diseases.

Each patient underwent a conventional 12-lead ECG, and, within minutes, underwent a lead 1

ECG rhythm recording using the iPhone based AliveCor application; ECG interpreted by two

cardiologists.

Out of 105 patients studied, 92 had normal sinus rhythm, 9 had atrial fibrillation, 2 had junctional

rhythm, and 2 had paced rhythm by a 12 lead electrocardiograph. An 83.8 percent correlation, 14.3

percent indeterminate, and 1.9 percent different diagnosis rate from the AliveCor heart monitor

compared to the 12-lead ECG was obtained. Out of 92 normal sinus rhythm cases, 88 percent

correlation, 11 percent indeterminate, and 1 percent different diagnosis rate was obtained. Out of

9 atrial fibrillation cases, 67 percent correlation, 22 percent indeterminate, and 11 percent different

diagnosis rate was attained.

The 16.2 percent of all cases that had either an indeterminate or inaccurate diagnosis from the

AliveCor Heart Monitor indicate substantial technical errors, most commonly caused by the

presence of baseline artifacts produced by a combination of movement, muscle tremor, and poor

contact surface. My findings suggest the use of alcohol swabs and electrode gel on patient hands

and AliveCor sensors limit baseline artifact.

After statistical analysis, values above a 95% confidence level for the Chi-squared method with

the statistically significant p-value of less than 0.001, estimates of population prevalence,

sensitivity, specificity, predictive values, and likelihood ratios, the study suggested the 83.8

percent correlation supports the hypothesis that an iPhone acquired heart rhythm can be used

reliably for clinical diagnosis of cardiac arrhythmias. My findings suggest the AliveCor application

can be used to recognize previously undiagnosed atrial fibrillation, allowing early initiation of

anticoagulants to prevent stroke.

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060

CLINICAL PERFORMANCE OF THE HEARTBUDS, AN ELECTRONIC

SMARTPHONE LISTENING DEVICE, COMPARED TO FDA CLASS I AND CLASS II

STETHOSCOPES R.S. Patel1, J.E. Schwarz1, V.C. Danesh3, A.M. Einhorn2, D. Bello1,2

1. University of Florida College of Medicine, Gainesville, FL, USA

2. Orlando Health Heart Institute, Orlando, FL, USA

3. Orlando Health Office of Research Operations, FL, USA

Background: Auscultation with stethoscopes is essential to the physical exam. However, the

stethoscope has not appreciably changed since Leared and Cammann developed the first binaural

stethoscopes in the mid 1800s. Because of technological advances, it is possible to use smartphone

technology to auscultate patients, and the HeartBuds, a listening device that integrates with an

iPhone app to achieve this purpose. The purpose of this study was to compare HeartBuds’ acoustic

superiority over the FDA approved class I blue disposable stethoscopes, which are commonly used

in practice to reduce hospital infection rates, and demonstrate equivalence to the gold standard

FDA class I analog stethoscope, the Littmann Cardiology III, and the FDA class II digital

stethoscope, the Littmann Electronic 3200.

Methods: 50 patients were auscultated with the above-mentioned stethoscopes. Two examiners

independently used these stethoscopes and rated their acoustic quality in addition to filling out

surveys documenting body sounds heard.

Results: The disposable stethoscope was significantly worse at identifying cardiac murmurs

(p<0.002), and performed poorly when auscultating for carotid bruits (p<0.058). The HeartBuds

was equivalent to its more commonly used counterparts, the Littmann Cardiology III and the

Littmann Electronic 3200. Examiners also found it to be of comparable acoustic quality to these

models.

Conclusion: HeartBuds is a smartphone compatible listening device that was superior in

examining cardiovascular sounds to approved FDA Class I disposable stethoscopes, and

equivalent to FDA approved class I and class II Littmann stethoscopes. Considering HeartBuds

equivalence to more expensive stethoscopes while costing much less, the HeartBuds can

potentially reduce infection rates without sacrificing quality. This can be achieved all while

reducing healthcare costs, which begs the question whether healthcare providers should rethink

using the device they have grown used to hanging around their necks.

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NEW INSIGHTS AND STRATEGIES FOR MYOCARDIAL REMODELING AND HEART FAILURE

061

VIEWING HEART FAILURE AS INTERSTITIAL CANCER: DIAGNOSTIC AND

THERAPEUTIC AVENUES

F.G. Spinale

University of South Carolina School of Medicine, Columbia, SC, and Wm. Jennings Bryan Dorn

VAMC, Columbia, SC, USA

In contrast to public perception, the morbidity and mortality as well as the resultant health care

costs associated with chronic heart failure (HF) are increasing and arguably reaching epidemic

proportions, but improvements in diagnostic and therapeutic strategies for this disease have not

been forthcoming. The factors that contribute to this relative paucity of new clinical tools for HF

are multifactorial but likely include the need to recognize and differentiate HF phenotypes and to

move beyond conventional thought regarding biological pathways, which regulate myocardial

growth and function. To that end, there are many lessons that can be learned from research in the

cancer field that are potentially translatable to the HF process. For example, the most numerous

cell type in the heart is the fibroblast, and with HF, this cell type undergoes a differentiation process

not dissimilar to that of cancer metastasis. Specifically, HF myocardial fibroblasts express

transcriptional and protein markers similar to those observed in a process of mesenchymal-

epithelial transformation described in cancer. Moreover, this laboratory and others have identified

proteolytic enzymes which degrade the tissue space - the extracellular matrix (ECM) emerges in

both patients and animal models of HF. The aims of this presentation will be 3-fold. First, examine

and identify the phenotype classifications of clinical HF and relate these phenotypes to

abnormalities in ECM and fibroblast growth and function. Second, present basic and translational

studies regarding fibroblast transformation in HF and pathways that may form therapeutic targets,

which may actually parallel chemotherapeutic strategies. Third, present new studies regarding

novel molecular imaging approaches and therapeutics for HF.

The conclusion to be drawn is that new findings in cancer research can be translated to target the

transdifferentiated fibroblast in HF as a form of interstitial cancer.

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062

BENDAVIA (MTP-131), A MITOCHONDRIA TARGETING PEPTIDE, NORMALIZES

DYSREGULATION OF MITOCHONDRIA FISSION AND FUSION PROTEINS IN

MYOCARDIUM OF DOGS WITH CHRONIC HEART FAILURE H.N. Sabbah, R.C. Gupta

Henry Ford Hospital, Detroit, Michigan, USA

Introduction: Studies of mitochondria (MITO) ultrastructure in heart failure (HF) reveal

considerable structural abnormalities along with marked hyperplasia and reduced organelle size.

MITO are highly dynamic organelles whose morphology, distribution and activity is regulated by

fission and fusion proteins that are also dysregulated in HF. We previously showed that chronic

therapy with Bendavia (BEN, MTP-131), a novel mitochondria-targeting peptide, improves LV

function in dogs with HF and normalizes MITO respiration and rate of ATP synthesis.

Objective: In this study, we tested the hypothesis that chronic therapy with BEN in dogs with HF

can reverse the dysregulation of MITO fission proteins (Fission-1, Fis1 and Dynamin-Related

Protein-1, Drp1) and fusion proteins (Mitofusin-2, Mfn2 and Dominant Optic Atrophy-1, OPA1)

in LV myocardium.

Methods: 14 HF dogs were randomized to 3 months therapy with subcutaneous injections of BEN

(0.5 mg/kg once daily, HF+BEN, n=7) or saline (HF-Control, n=7). LV tissue was obtained from

all dogs at end of therapy and from 6 normal (NL) dogs for comparison. Protein level of Fis1 and

Drp1 and of Mfn2 and OPA1 was measured with specific antibodies using Western blotting. In

addition Porin, a MITO protein that is unaltered in HF, was also measured as internal control and

all bands were quantified in densitometric units (du).

Results: Porin level was unchanged among the 3 study groups. Compared to NL, levels of Mfn2

and OPA1 were significantly reduced, and levels of Fis1 and Drp1 were significantly increased in

HF-Controls. BEN restored protein levels of OPA1, Mfn2, Fis1, and Drp1 to near normal.

Conclusions: Long-term therapy with BEN reversed the dysregulation of MITO fission and fusion

proteins in LV myocardium of dogs with HF. These findings support the observations of improved

MITO respiration and rate of ATP synthesis and the improved LV function seen in dogs with HF

after chronic treatment with BEN.

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063

GENE-TARGETING OF NATRIURETIC PEPTIDE RECEPTOR-A ENHANCES THE

EXPRESSION OF RAAS COMPONENTS LEADING TO INFLAMMATORY

HYPERTENSIVE HEART DISEASE

K.N Pandey

Tulane University Health Sciences Center, New Orleans, LA, USA

Atrial natriuretic peptide (ANP) was discovered over 30 years ago in the atrium of heart and has

been extensively investigated with regard to physiology, pathophysiology, and cardiovascular

disease therapeutics. ANP and brain natriuretic peptide (BNP) bind to guanylyl cyclase-

A/natriuretic peptide receptor-A (GC-A/NPRA), which produces the intracellular second

messenger cGMP and exhibit diuretic, natriuretic, and vasorelaxant effects with novel properties,

including antihypertrophic, antifibrotic, antiproliferative, and antiinflammatory actions with a

pivotal role in cardiovascular remodeling. GC-A/NPRA signaling antagonizes the cellular and

physiological effects mediated by the renin-angiotensin-aldosterone system (RAAS). Genetic

disruption of Npr1 (coding for GC-A/NPRA) increases 35-40 mmHg higher systolic blood

pressure and a 63% greater heart weight/body weight (HW/BW) ratio leading to congestive heart

failure in null mutant (Npr1-/-) mice compared with wild-type (WT; Npr1+/+) mice. The

expression levels of angiotensin-converting enzyme (ACE) and angiotensin II type 1a receptor

(AT1a) mRNA were increased by 4- to -5fold in Npr1-/- mice hearts compared with the WT mice

hearts. The cardiac angiotensin II and aldosterone levels were also significantly increased in Npr1-

/- mice than WT controls. Concomitantly, the expression of interleukin-2 (Il-2), interleukin-6 (IL-

6), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-β1 (TGF-β1) were

also increased by 4- to 5-fold, in null mutant mice hearts as compared with WT mice. The

expression of nuclear factor-kappa B (NF-kB) and its binding activity in the nuclear extracts of

Npr1-/- mice hearts was increased by 3- to 4-fold compared with WT mice. Treatment with

captopril or hydralazine equally reduced the blood pressure, but only captopril significantly

decreased the HW/BW ratio and proinflammatory cytokine gene expression in Npr1-/- mice hearts.

The results suggest that the disruption of ANP/NPRA/cGMP signaling leads to augmented

expression and activation of RAAS-mediated signaling pathways that enhance the expression of

proinflammatory cytokines and promote cardiac hypertrophy, dysfunction, and heart failure.

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064

ALTERED NUCLEAR AND CYTOSKELETAL MECHANICS IN CARDIAC

MYOCYTES WITH D192G NUCLEAR LAMIN MUTATION C.S. Long1, L. Mestroni1, O. Sbaizero2

1. University of Colorado, Denver, CO, USA

2. University of Trieste, Trieste, Italy

Atomic force microscopy whole-cell loading/unloading curves were used to study the mechanical

behavior of cardiomyocytes carrying the LMNA D192G mutation which is known to cause a

severe form of dilated cardiomyopathy. Here, combining atomic force microscopy (AFM) with

molecular and cellular biology methodologies, we studied both nuclear and whole-cell

biomechanical behavior in Neonatal rat ventricular myocytes (NRVMs) expressing the LMNA

D192G mutation and compared this with both control cells and those expressing wild-type LMNA.

LMNA protein expression was confirmed up to day 6. Live-cell AFM force-deformation curves

from days 1 through 6 showed that LMNA D192G nuclei displayed increased stiffness compared

to controls with a peak at 72 hours (p < 0.05), with a 3 time increase in nuclear Young modulus.

Furthermore, mutant NRVMs showed an unexpected reduction in the adhesion area between AFM

probe and cell membrane compared to control and wild-type. Finally, D192G NRVMs displayed

altered cytoskeletal deformation measured as force decays with time (relaxation force test)

compared to wild-type and control NRVMs, suggesting loss of cytoskeleton elasticity. The altered

mechanical behavior of LMNA D192G NRVMs was rescued by wild-type LMNA expression in

mutant cells. Our results suggest that the LMNA D192G mutation has a profound effect on the

whole-cell biomechanics in cardiomyocytes, extending beyond the increased nuclear stiffness,

indicating cytoskeletal structural modifications and reduced cell membrane adhesion, changes that

can be rescued by wild-type LMNA. These findings extend our understanding of the

pathophysiology of this, and perhaps other, gene-specific causes of cardiomyopathy and provide

a cell-based assay for their analysis and potential novel therapies.

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065

MOLECULAR REGULATION OF DOXORUBICIN INDUCED HEART FAILURE R. Dhingra1, V. Margulets1, D. Jassal1, G. Dorn II2, L.A. Kirshenbaum1

1. The Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, Departments

of Physiology Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

2. Department of Internal Medicine, Washington University School of Medicine, St. Louis MO,

USA

Doxorubicin is known for its cardiotoxic effects and inducing cardiac failure, however, the

underlying mechanisms remain cryptic. Earlier we established the inducible - death protein, Bcl-

2-like Nineteen- Kilodalton- Interacting - Protein 3 (Bnip3) to be crucial for disrupting

mitochondrial function and inducing cell death of cardiac myocytes. Whether Bnip3 underlies

cardiotoxic effects of doxorubicin toxicity is unknown. Herein we demonstrate a novel signaling

pathway that functionally links activation and preferential mitochondrial targeting of Bnip3 to the

cardiotoxic properties of doxorubicin. Perturbations to mitochondria including increased calcium

loading, ROS, loss of mitochondrial membrane potential and mPTP opening were observed in

cardiac myocytes treated with doxorubicin. In mitochondria, Bnip3 forms strong association with

Cytochrome c oxidase subunit1 (COX1) of respiratory chain and displaces uncoupling protein 3

(UCP3) resulting in increased ROS production, decline in maximal and reserved respiration

capacity and cell viability. Impaired mitochondrial function was accompanied by an accumulated

increase in autophagosomes and necrosis demonstrated by increase release of LDH, cTnT and loss

of nuclear High Mobility Group Protein 1 (HMGB-1) immunoreactivity. Interestingly,

pharmacological or genetic inhibition of autophagy with 3-methyl adenine (3-MA), or Atg7 knock-

down suppressed necrotic cell death induced by doxorubicin. Loss of function of Bnip3 restored

UCP3-COX complexes, mitochondrial respiratory integrity and abrogated necrotic cell death

induced by doxorubicin. Mice germ-line deficient for Bnip3 were resistant to doxorubicin

cardiotoxicity displaying normal mitochondrial morphology, cardiac function and survival rates

comparable to vehicle treated mice. The findings of the present study demonstrate that doxorubicin

provokes maladaptive autophagy and necrotic cell death of ventricular myocytes that is mutually

dependent and obligatorily linked to Bnip3.

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066

CALCIUM SIGNAL, TRANSCRIPTION AND DCM

B. Tuana

University of Ottawa Heart Institute, Ottawa, ON, Canada

Cytosolic calcium levels critically determine and contraction/relaxation cycle of cardiomyocytes.

The calcium signals also regulate cardiac cell growth through gene/protein expression. The

calcium signal is translated through calcium binding proteins and phosphorylation mechanisms at

the level of the contractile machinery and the cardiac genome. In particular a family of protein

kinases (PKs) activated by calcium and calmodulin (CaM) has been shown to translate the calcium

signal to promote cardiac growth and modulate contractile state. Data on the distinct members of

the calmodulin activated protein kinases and how there activity impacts cardiac dysfunction,

ventricle dilation and growth will be discussed with a view to design novel therapy.

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067

THE ROLE OF MICRORNAS IN PERIPARTUM CARDIOMYOPATHY

N. Nair

Providence Sacred Heart Medical Center, Spokane, WA, USA

Peripartum cardiomyopathy (PPCM) causes considerable morbidity and mortality in young

women during their reproductive years. The presentation is usually in the month preceding

delivery up to 5 weeks post-partum. This overview will address some of the new developments in

the field of molecular medicine using micro RNAs for diagnosis and also as therapeutic targets.

In normal pregnancy reactive oxygen species increases ROS production reverting to normal levels

in the post-partum period .However the total anti-oxidant capacity also increases during pregnancy

and continues to be elevated post-partum. Studies on mice with Stat3 deletion have revealed the

link between oxidative stress and prolactin. The increase in reactive oxygen species (ROS) in this

murine model was associated with cleavage of the hormone prolactin (PRL) by ROS-activated

Cathepsin D. These mice showed increased expression/activity of cathepsin D associated with the

generation of a cleaved antiangiogenic and proapoptotic 16 kDa form of prolactin. Bromocriptine

prevented PPCM in the STAT3 deleted mice. The 16 kDa form of prolactin impaired the cardiac

capillary network and function in the myocardium resulting in the cardiac phenotype of PPCM.

The micro RNA mir146-a has been implicated in the regulation of the prolactin signaling pathway.

The 16K prolactin fragment exerts negative effects in endothelial cells by up regulating miR-146a.

Additionally mir-146a levels were increased in patients with PPCM which resolved after treatment

with bromocriptine possibly defining the role of prolactin in the pathophysiology of PPCM.

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ARRHYTHMIA, ELECTROPHYSIOLOGY AND STROKE PREVENTION

068

ARRHYTHMIAS IN ADULT CONGENITAL HEART DISEASE

C.I. Berul

Children's National Medical Center, George Washington University,

Washington, DC, USA

There are now more adults living with congenital heart disease (CHD) than children with CHD,

due to the remarkable improvements in medical, interventional, and surgical care of these complex

patients. However, despite increased survival and longevity, the long-term hemodynamic

abnormalities and suture lines leave these patients with substantial electrophysiological sequelae.

The vulnerability to sinus and atrioventricular nodal dysfunction increases risk of eventual need

for permanent pacing, while atrial and ventricular tachyarrhythmias may develop due to the

underlying anatomic substrates, which may lead to the need for catheter ablation procedures and/or

implantable cardioverter defibrillators. Systemic ventricular dysfunction may also be treated with

cardiac resynchronization pacing. These electrophysiologic interventions may require special

circumstances and unique treatments due to variations in venous and cardiac anatomy. For

example, transvenous access may not be feasible for adults with CHD who have interrupted vena

cava, single-ventricle Fontan physiology, or other congenital anomalies or surgically-acquired

obstructions. Unique routes of implantation may be necessary for placement of pacemakers,

defibrillators, and resynchronization leads. Epicardial access may also be challenging, due to prior

cardiac surgeries, adhesions, and congenital anomalies. Therefore, novel approaches and hybrid

procedures may be indicated for electrophysiological interventions in adults with congenital heart

disease. These procedures should be performed at regional expert centers of adult CHD care, by

electrophysiologists experienced in congenital heart disease. Knowledge of the detailed anatomy

and surgical procedures is necessary to fully understand the nuances of performing these

procedures, and pre-intervention imaging is helpful to delineate the electrophysiologic procedural

plan. Despite the additional complexities, with proper planning and collaboration, an experienced

adult CHD team can provide excellent electrophysiological outcomes.

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069

THE 2014 AF GUIDELINES: WHAT'S NEW?

M.E. Cain

University at Buffalo, Buffalo, NY, USA

The 2014 AHA/ACC/HRS Guidelines for the management of patients with atrial fibrillation (AF)

are derived from published clinical trials, basic science, and comprehensive review articles. They

supersede the ACC/AHA/ESC 2006 Guidelines and two subsequent focused updates from 2011.

Key new recommendations impacting patient care are: 1) usage (Class I) of the CHA2DS2-VASc

score to assess risk of stroke in patients with nonvalvular AF; 2) usage (Class I) of oral

anticoagulation (warfarin, dabigatran, rivaoxaban, or apixaban) for patients with nonvalvular AF

with a history of stroke, transient ischemic attack, or a CHA2DS2-VASc score of 2 or greater; 3)

omission (Class IIa) of antithrombotic therapy for patients with nonvalvular AF and a CHA2DS2-

VASc score of 0; 4) for patients with nonvalvular AF and a CHA2DS2-VASc score of 1, choice

(Class IIb) of no antithrombotic therapy, oral anticoagulation, or aspirin; 5) avoidance (Class III

harm) of dabigatran, rivaroxaban, or apixaban for patients with AF and a mechanical or

bioprosthetic heart valve; 6) avoidance of flecainide, propafenone, dofetilide, and sotalol in

patients with severe left ventricular hypertrophy and AF; 7) prescription (Class I) of oral

anticoagulation for patients with hypertrophic cardiomyopathy and AF irrespective of CHA2DS2-

VASc score; 8) catheter ablation is useful (Class I) for patients with symptomatic, paroxysmal, AF

who have not responded to or tolerated antiarrhythmic medications; and 9) catheter ablation is

reasonable (Class II) in selected patients with symptomatic, paroxysmal, AF prior to a trial of

medical therapy, provided it can be performed at an experienced center.

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070

GLOBAL ATRIAL FIBRILLATION BURDEN: PREVENTION RATHER THAN

TREATMENT MUST BE THE GOAL!

K. Seidl

Medizinische Klinik IV, Ingolstadt, Germany

The estimated number of individuals with AF globally in 2010 was 33.5 million (20.9 million men]

and 12.6 million women. Burden associated with AF, measured as disability-adjusted life-years,

increased by 18.8 in men and 18.9% in women from 1990 to 2010. In 1990, the estimated age-

adjusted prevalence rates of AF (per 100 000 population) were 569.5 in men and 359.9 in women.

Mortality associated with AF was higher in women and increased by 2-fold and 1.9-fold in men

and women, respectively, from 1990 to 2010. There was evidence of significant regional

heterogeneity in AF estimations. The incidence of atrial fibrillation is twice as high in developed

countries compared to the developing countries. The increase of AF incidence was 70% in the

developed countries compared to only 11 % in the developing countries.

There are several risk factor for atrial fibrillation which could be influenced: obesity, diabetes,

hypertension, inflammation, and sleep apnea. Weight reduction and cardiometabolic risk factor

management can reduce the burden of atrial fibrillation. In addition the recurrence rate could be

reduced with an intensive cardiometabolic risk factor management either after pharmacological

treatment or after catheter ablation of AF

Conclusion: These findings provide evidence of progressive increases in overall burden, incidence,

prevalence, and AF-associated mortality between 1990 and 2010, with significant public health

implications. Cardiometabolic risk factor management can further reduce the burden of atrial

fibrillation in addition to conventional treatment options.

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071

HYBRID ATRIAL FIBRILLATION FOR ADVANCED ATRIAL FIBRILLATION

A. Khoynezhad

Cedars-Sinai Medical Center, Los Angeles, CA, USA

Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with a nearly

five-fold increased risk for stroke as well as over two-fold increased risk of death. For symptomatic

drug-refractory AF, percutaneous ablation has been used with good success in paroxysmal AF. For

patients with persistent AF, the results of catheter ablation are not very good. Surgical AF using

minimal-invasive approaches may be offered to this cohort. We analyzed our data in

thoracoscopically-performed ablation of AF on the beating heart, and found this to be technical

feasible, achieving high success rates with low procedure-related morbidity in early follow-up.

The next frontier in treatment of atrial fibrillation is hybrid atrial fibrillation. This is the most

aggressive and arguably the most effective approach in advanced AF. The patient undergoes

initially a thoracoscopic Maze with complex left atrial lesion set. At three months, an EP evaluation

of the left atrial lesions are performed, and additional lesion performed as needed. Furthermore,

the right-sided isthmus lesion is performed. The results of the hybrid approach are discussed along

with on-going DEEP trial investigating global outcome with hybrid Maze.

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072

LEFT VENTRICULAR REVERSE REMODELING WITH BIVENTRICULAR VERSUS

RIGHT VENTRICULAR PACING IN PATIENTS WITH ATRIOVENTRICULAR

BLOCK AND LEFT HEART FAILURE IN THE BLOCK HF TRIAL M. St. John Sutton1, A.B. Curtis2, S.J. Worley3, T. Plappert1, P.B. Adamson4,

E.S. Chung5

1. University of Pennsylvania, Philadelphia, PA, USA

2. University at Buffalo, Buffalo, NY, USA

3. Lancaster General Hospital, Lancaster, PA, USA

4. Oklahoma Foundation for Cardiovascular Research, Oklahoma City, OK, USA

5. The Heart and Vascular Center at The Christ Hospital, Cincinnati, OH, USA

Background: In patients with heart failure (HF), biventricular pacing (BIV) attenuates adverse left

ventricular (LV) remodeling in addition to improving survival and relieving symptoms. However,

little is known about the effects of BIV pacing in HF patients with atrioventricular (AV) block.

Methods: The BLOCK HF trial randomized patients with AV block, NYHA class I-III heart

failure, and LV ejection fraction (EF) less than or equal to 50% to BIV or right ventricular (RV)

pacing. Doppler echocardiograms (DE) were obtained at randomization (30-60 days post-implant)

and at 6, 12, 18, and 24 months. Data analysis comparing changes in 10 pre-specified echo

parameters over time was conducted using a Bayesian adaptive design and all objectives were

evaluated with intention-to-treat analyses. Results: There were 624 subjects among the 691

randomized subjects who had paired DE data for one or more analyses. LV volumes, EF, diastolic

function and intra-ventricular mechanical delay (IVMD) were estimated at all time points. BIV

pacing resulted in LV reverse remodeling, with significant reduction in LV end systolic and end

diastolic volume indices and in IVMD and improvement in EF. By contrast, none of these

parameters changed with RV pacing, indicating that no reverse remodeling occurred post-

randomization.

Conclusions: Patients with AV block, depressed LV function, and HF symptoms benefit from BIV

pacing with regard to cardiac structure and function. This DE analysis has important clinical

implications in supporting the use of BIV pacing rather than RV pacing for patients with HF and

AV block.

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073

SYNCOPE VS PSEUDOSYNCOPE: DIFFERENTIATION, DIAGNOSIS AND

TREATMENT J. Robinson, C. Snyder

Case Western Reserve University School of Medicine, Rainbow Babies and Children's Hospital,

Cleveland, OH, USA

Background: Syncope is common in the pediatric population. Pseudosyncope (PS) can be difficult

to distinguish from classical syncopal episodes. Head-up tilt table (HUTT) has been employed as

a diagnostic test for PS in adults; however, its use in the pediatric population is currently not

described. The purpose is to describe the diagnostic utility of HUTT to elicit the diagnosis of PS

in the pediatric population.

Design/Methods: A retrospective chart review from 11/12 to 10/14 of all patients less than 23 yrs

of age referred for HUTT, consisting of a 30-minute, 80-degree HUTT with continuous monitoring

of ECG and pulse ox. Blood pressure and heart rate were obtained supine, at 80-degree tilt, and

every minute. Symptoms were recorded with vital signs taken concurrently.

Results: 51 patients were referred for HUTT [median age 16 yrs (5-23); 13 (25%) male]. The

majority (27, 53%) had a negative HUTT , 24 had a positive HUTT, (vasovagal 13, postural

orthostatic tachycardia syndrome 4, and idiopathic 3 . The remaining 4 (17%) were diagnosed

with PS [median age 16 yrs (15-17); 1male]. Pretest probability for PS was high 1) failed

appropriate management, 2) atypical episodes, 3) occurrence during exercise, or 4) prolonged

duration. Due to high suspicion, prior to HUTT the likelihood of episode was discussed with

patient. Episodes of PS occurred: 2 had PS within 2 minutes and 2 had episodes > 15 minutes into

HUTT. PS was verified by normal vital signs and disruptive maneuvers: verbal response to

questions, hand clap, sternal rub.

Conclusions: PS should be considered in patients that have failed appropriate management or who

exhibit atypical episodes of syncope. PS can be identified with a HUTT if specific prompting of

patients is utilized. Disruptive maneuvers, hand clap, sternal rub, etc., are excellent adjuncts to

confirm diagnosis.

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074

SUCCESS OF ATRIAL FIBRILLATION ABLATION IN VARIOUS SUBSETS

K. Srivathsan

Mayo Clinic, AZ, USA

Atrial fibrillation is an increasingly common clinical problem as the age of the population in North

America has significantly increased. Medical therapy in terms of stroke prevention is improving.

However, rhythm restoration is undergoing significant research and evolution. Medications to

restore sinus rhythm have been minimally effective and therefore, invasive strategies such as

percutaneous ablation have become increasingly common. Percutaneous ablation is seems to be

more effective in certain sub groups such as shorter duration of disease, no structural heart disease

and no significant valvular heart disease. Identifying success of the ablation in various sub groups

is critical for good clinical outcome.

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075

ZHANG’S PHENOMENON (HIS ELECTROGRAM ALTERNANS) AND A NEW

MODEL OF ATRIOVENTRICULAR NODE DUAL PATHWAY CONDUCTION

Y. Zhang

Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic

Medicine, Old Westbury, NY, USA

Zhang’s phenomenon (originally His electrogram alternans), a new index of dual pathway

atrioventricular (AV) node conduction, indicates that there are dual inputs rather than a final

common pathway from the AV node into the His bundle. Our recent data revealed that during fast

pathway (FP) conduction, the electrical excitation in the AV node propagates in a superior to

inferior direction across the AV conduction axis. In contrast, this superior-inferior activation fails

within the superior nodal domain during slow pathway (SP) conduction. This then permits

electrical excitation to proceed longitudinally along the AV conduction axis through the inferior

nodal domain. This transverse versus longitudinal electrical propagation in the AV node produces

superior-fast and inferior-slow dual inputs into the His bundle during dual pathway conduction

(the electrophysiological basis of Zhang’s phenomenon). We believe that the peculiar anatomical

location and fiber orientation of the AV node are mainly responsible for the unique electrical

conduction pattern. The AV node is open only superiorly and posteriorly to atrial excitation. Fibers

inside the AV node are largely aligned longitudinally along the AV conduction axis. Electrical

propagation across fiber orientation (in a superior to inferior direction) is possible during FP

conduction. However, this cross-fiber activation results in a longer effective refractory period and,

thus, this activation will fail at short prematurities (i.e., SP conduction). Longitudinal activation

along the fiber orientation results in a short effective refractory period. The failing of superior-

inferior activation permits excitation to proceed along fiber orientation in the inferior nodal domain

during SP conduction (i.e., at short prematurities). In summary, the transverse versus longitudinal

electrical propagation within the AV node, the resulting functional dissociation in the distal node,

and the superior-fast and inferior-slow dual inputs into the His bundle form the main features of

the new model of dual pathway AV conduction.

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076

LONG TERM OUTCOMES OF SURGICAL AF ABLATION: ASSESSMENT OF

EFFICACY USING IMPLANTABLE CARDIAC MONITORS C. Castellani, M. Viqar, D. Gandhi, D. Grimes, J. Boak, J. Ip

Michigan State University, East Lansing, MI, USA

Background: Pulmonary Vein Isolation (PVI) is an effective treatment in recurrent atrial

fibrillation (AF). However, no consensus exists on the definition of PVI success. Existing data are

limited to intermittent holter or event recordings with reliance on patient symptoms.

Objective: We sought to determine the outcomes of surgical PVI and post ablation AF surveillance

with implantable cardiac monitors (ICM) (Reveal XT, Medtronic Inc.). Methods: We designed a

prospective study using ICM with an inherent algorithm for automatic recognition and detection

of AF post PVI and followed patients to assess the natural course of AF recurrence. AF recurrence

was defined as weekly AF burden > 5% as recorded by the ICM within a 3 month rolling window.

Consecutive 65 patients underwent limited thoracotomy, video assisted epicardial PVI, were

implanted with cardiac monitors and were followed. Data was downloaded weekly using

CareLink® system. All transmitted events were analyzed for arrhythmias.

Results: 65 patients were followed after PVI for a mean of 27 ± 2 months. AF recurrence was

highest in first 3 months (68%) and substantially decreased over 12 months (22%) post PVI.

However, late AF recurrence was common. Overall freedom from AF recurrence at follow-up

completion (27 months) was 48%.

Conclusions: Our study is unique in using ICM after ablation to obtain an objective measurement

of success. Late recurrence of AF is common but not associated with symptoms in a significant

percentage of patients. ICM should be considered standard for future studies aimed at defining

success of AF ablation procedures.

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89


ASSESSMENT AND MANAGEMENT OF CARDIOVASCULAR RISK / MODIFICATION OF LIPOPROTEINS

077

LIFE-EXPECTANCY DIFFERENCES BETWEEN OLYMPIC HIGH JUMPERS AND

DISCUS THROWERS

J. Lee-Heidenreich, J. Myers

VA Palo Alto Health Care System, Palo Alto, CA and Stanford University, Stanford CA, USA

Background: Several studies have demonstrated that body habitus is associated with survival. We

sought to determine if survival differed between elite ectomorph (high jump) and mesomorph

(discus) athletes.

Methods: For each Olympics between 1924 and 1948 we identified the top (up to 20) Olympic

male and female finishers in the high jump (HJ) and the discus. We determined date of death using

internet searches and calculated age-specific expected survival using published US life tables. We

adjusted life-expectancy for country of origin based on Global Burden of Disease data.

Results: We identified a death date for 182 of 224 (81%) Olympic athletes (61 male HJ, 59 male

discus, and 32 female HJ, 30 female discus). Discus throwers were older during the Olympics by

a mean of 2.8 ± 0.6 years, p<0.0001), heavier by 33 ± 4 lbs, p<0.0001, and taller by 0.9 ± 0.4

inches, p=0.04. Survival was higher for HJ (Figure). Observed-expected survival was 8.9±14.8

years for HJ and 5.0±13.5 years for discus athletes (p=0.06). In multivariate analysis, mortality

was lower for HJ compared to discus throwers (HR 0.64, 95% CI 0.46-0.88, p=0.006) after

adjustment for age, year of Olympics, and gender. However, after additional adjustment for

weight, the effect of HJ was no longer significant (HR 0.89, 95% CI 0.56-1.40, p=0.61).

Conclusion: We found that elite high jumpers live longer than elite discus throwers, and this is

explained in large part by body habitus (weight).

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078

CHOLESTEROL GOALS & TARGETS: SHOULD WE IMPROVE-IT?

L. Sperling

Emory University School of Medicine, Atlanta, GA, USA

Appropriate intensity statins are recommended by the ACC/ AHA Blood Cholesterol Guidelines

as first line lipid therapy for both high risk secondary prevention patients with established

atherosclerotic cardiovascular disease (ASCVD) and post-acute coronary syndrome (ACS). The

IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) is the first

randomized prospective clinical outcomes trial to demonstrate that stain therapy plus a non-statin

agent (ezetimibe) reduced ASCVD events (6.4% relative risk reduction of the primary composite

endpoint). It is likely this study will impact future guideline recommendations. Despite

established benefits of statin therapy for secondary prevention there appears to be substantial

underutilization of well-validate guideline-directed therapies, and a significant lack of medication

adherence. Strategies to assess gaps in care delivery, improve awareness of guideline-driven

recommendations, and patient adherence to therapies may be more important ways to IMPROVE-

IT.

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079

THE EFFECTS OF PLANT-BASED, MEDITERRANEAN, PALEOLITHIC, AND DASH

DIETS ON CARDIOVASCULAR DISEASE RISK A.J. Allen, D.R. Talreja, H.A. Buchanan, J. Wetmore, D. Winegar

Eastern Virginia Medical School, Norfolk, Virginia, USA

Background: Cardiovascular disease (CVD) is the leading cause of death in the United States for

middle-aged men and women despite the fact that prevention and control of CVD is achievable by

modifying risk factors through lifestyle changes and diet therapy. We examined the impact of four

diet programs (plant-based (Vegan), Mediterranean, Paleolithic (Paleo) and DASH diets) on the

CV risk factor profile of adults in the Hampton Roads area of Virginia.

Methods: Nondiabetic adults (ages 35-85) with one or more risk factors for CVD were invited to

participate in 1 of the 4 diet arms. Participants underwent a comprehensive nutrition education

program prior to 60-day diet intervention in which they kept daily food logs and met weekly with

a multi-disciplinary study team. An initial health screen was performed to assess weight, blood

pressure (BP), fasting glucose (FPG), A1C, lipids and lipoprotein particles, and repeated after 60

days on the diet and at 6-months follow-up.

Results: 279 subjects completed the 60-day dietary intervention (58 Vegan, 80 Mediterranean, 76

Paleo, 65 DASH), and 199 returned for 6-month follow-up. Most subjects were female, Caucasian,

mean age 56, mean BMI 33 kg/m2. At baseline, mean FPG, TG and HDL-C were within the

normal range, whereas LDL-P and BP were elevated. After 60 days on the respective diets, subjects

lost an average of 9 lbs (4.7% body weight, total 2,576 lbs), which was associated with

improvements in BP across all groups. Subjects on the Vegan and Paleo diets lost the most weight

(6.5%) and showed the greatest improvement in lipid risk factors (11-14% decrease in LDL-P; 10-

20% decrease in VLDL and TG).

Conclusion: All four diets promoted weight loss and improved BP but had variable effects on

lipid risk factors. Effects were greatest and sustained in those subjects that attended regular diet

support group meetings.

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080

QUANTIFYING THE ASSOCIATION BETWEEN PHYSICAL ACTIVITY AND

CARDIOVASCULAR DISEASE: A META-ANALYSIS A.A. Wahid1, N. Manek2, M. Nichols4, P. Kelly5, C. Foster3, P. Webster6, A. Kaur3,

C. Friedemann Smith3, P. Scarborough3 1. University of Oxford, Oxon, UK

2. Watford General Hospital, Imperial College Healthcare NHS Trust, London, UK

3. The British Heart Foundation Centre on Population Approaches for Non-Communicable Disease

Prevention, Department of Public Health, University of Oxford, UK

4. WHO Collaborating Centre for Obesity Prevention, Deakin University, Geelong, Australia

5. Sport, Physical Education and Health Sciences Department (SPEHS), University of Edinburgh, UK

6. University of Oxford Public Health Department, UK

Background and objective: The relationships between physical activity (PA) and cardiovascular

disease (CVD) have predominantly been estimated using categorical measures of PA. In this

systematic review and meta-analysis we derive a single continuous physical activity metric to

directly compare the association between activity and CVD, both before and after adjustment for

a measure of body weight.

Data sources: A systematic review was conducted through searching electronic databases such as

MEDLINE and EMBASE for studies published between 1981 and 2014.

Study eligibility criteria and participants: Prospective cohort studies were included that measured

PA levels where at least two of the following domains were measured: leisure, active travel and

occupational activity. The relative risk needed to have been reported in healthy individuals and

been adjusted for a measure of body weight. The PA exposure in each study was converted to

MET hours per day. Various transformations were explored to parametrically describe the dose-

response relationships, as well as a non-parametric categorical approach.

Results: A total of thirty-six studies were included in the analysis. An increase from inactive to

achievement of recommended PA levels 150 minutes of moderate-intensity aerobic activity

reduced the risk of CVD mortality by 23% and CVD incidence by 17% (RR 0.77 (0.71-0.84) and

(RR 0.83 (0.77-0.89) respectively, after adjustment for body weight. Overall, there were a total of

3,439,874 participants, with 179,393 events occurring during an average follow up period of 12.3

years.

Conclusions: and implications: A single continuous metric for PA levels allowed us to directly

compare the effect of physical activity on CVD incidence and mortality including myocardial

infarct (MI), coronary heart disease (CHD) and heart failure. Effect sizes suggested that the

greatest gain in health is associated with moving from inactive to small amounts of physical

activity.

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081

ASPIRIN FOR PRIMARY PREVENTION OF CARDIOVASCULAR AND ALL-CAUSE

MORTALITY: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS A. Alrifai1, S. Al Halabi2, R.S. Rosenstein3

1. University of Miami Miller School of Medicine, Regional Medical Campus, Atlantis, FL,

USA

2. Cleveland Clinic Foundation, Cleveland, OH, USA

3. Veterans Affairs Medical Center West Palm Beach, West Palm Beach, FL, USA

Objectives: To assess the safety and impact of aspirin on cardiovascular outcomes in primary

prevention.

Background: The use of aspirin in primary prevention without established coronary heart disease

is still controversial. We performed a meta-analysis of randomized controlled trials (RCTs)

comparing Aspirin to placebo for the primary prevention of cardiovascular events and mortality.

Methods: We searched PubMed, Medline, Embase and Cochrane for RCTs that compared Aspirin

versus placebo in patients without established coronary artery disease. Trials that included patients

with or without cardiac risk factors who were randomized to either Aspirin or placebo and that

reported at least one of the studied outcomes were included. Study quality was assessed using the

Jadad score. Heterogeneity of the studies was analyzed by Cochran’s Q statistics. Mantel Haenszel

relative risk and mean difference were calculated using the random effect model.

Results: Ten RCTs met our inclusion criteria and included 113900 patients with hypertension,

dyslipidemia, tobacco smoking, or diabetes mellitus. The use of Aspirin was associated with lower

non-fatal myocardial infarctions (MI) when compared to placebo (RR 0.79; 95% CI 0.64 –0.97;

P=0.03). No significant difference in the incidence of fatal MI (RR 0.99; 95% CI 0.75 –1.29;

P=0.92) or cardiovascular mortality (RR 0.95; 95% CI 0.83 –1.08; P=0.42) was observed between

the two groups. There was an increase in the overall bleeding with the use of aspirin compared to

placebo. (RR 1.33; 95% CI 1.16 –1.53; P<0.001). Lower all-cause mortality was noted in the

Aspirin group compared to placebo (RR 0.94; 95% CI 0.89 –1.00; P=0.04).

Conclusions: Our findings suggest that the use of Aspirin in primary prevention is associated with

a reduction in non-fatal MI and all-cause mortality at the cost of increased risk of bleeding. The

use of aspirin should be made on a case-by-case basis.

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082

RISK OF MYOCARDIAL INFARCTION AND STROKE IN WOMEN WITH FAMILY

STRESS IN GENERAL POPULATION 25-64 YEARS IN RUSSIA: WHO

EPIDEMIOLOGICAL PROGRAM MONICA-PSYCHOSOCIAL V. Gafarov1,2, D. Panov2, E. Gromova2, I Gagulin1,2, A. Gafarova1,2

1. Collaborative Laboratory of Cardiovascular Diseases Epidemiology SB RAMS, Novosibirsk,

Russia

2. FSBI Institute of Internal and Preventive Medicine SB RAMS, Novosibirsk, Russia

Objective: To explore the influence of family stress on relative risk of myocardial infarction (MI)

and stroke in female population aged of 25-64 years in Russia over 16 years of follow-up.

Methods: Under the third screening of the WHO "MONICA-psychosocial" (MOPSY) program

random representative sample of women aged 25-64 years (n=870) were surveyed in Novosibirsk.

Questionnaire MOPSY was used for assessment of family stress. From 1995 to 2010 women were

followed for the incidence of stroke and MI with using “Myocardial Infarction Registry” data. Cox

regression model was used for relative risk assessment (HR) of MI, stroke.

Results: The prevalence of high family stress level in women aged 25-64 years was 20.9%. HR of

MI over 16 years of follow-up in women with family stress was 5.59-fold higher (95.0%CI:1.99-

15.70, p=0.001) compared to those without stress. HR of stroke in women with family stress was

3.53-fold higher (95.0%CI:1.82-6.84, p<0.001). There were tendencies of increasing MI and

stroke rates in married women experienced stress in family compared to divorced and widowed

with the same stress level. As the tendency a stroke more likely developed in women with high

and elementary school education having family stress. With regard to occupational class the

tendency of higher stroke rates was found for “physical workers” with family stress compared to

those without it (÷2=3.69 df=1 p=0.055) and MI rates were tend to be higher in “managers” and

“engineers” experienced stress in family.

Conclusions: The prevalence of high stress in family in female population aged 25-64 years is

more than 20% in Russia. Women with high family stress had significantly higher relative risk of

MI and stroke over 16-th years of follow-up. Rates of MI and stroke development were more likely

in married women with low educational level and high family stress in professional class

“managers” and “physical laborers”.

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083

DECREASED SERUM VASPIN LEVELS ARE ASSOCIATED WITH CORONARY

ARTERY DISEASE: A META-ANALYSIS P. Agasthi1, A. Chenna1, P. Kudaravalli3, S. Aloor2, A. Onwuanyi1

1. Morehouse School of Medicine, Atlanta, Georgia, USA

2. Miller School of Medicine, University of Miami, Miami, Florida, USA

3. University of Nevada School of Medicine, Reno, Nevada, USA

Background: Vaspin is a serine protease inhibitor and a newly identified adipokine linked with

obesity and insulin sensitivity. Vaspin is shown to exert anti-inflammatory and anti-apoptotic

effects on endothelial cells and vascular smooth muscle cells via inhibition of NADPH oxidase

mediated production of reactive oxygen species. The association between serum vaspin and

coronary artery disease (CAD) is obscure.

Objective: The aim of the present study is to conduct a meta-analysis to evaluate the relationship

between serum vaspin levels and CAD.

Methods: We searched MEDLINE, CINHAL and COCHRANE databases for studies reporting

serum vaspin levels in the CAD and non CAD study population. We included case controls, cohort

and cross-sectional studies. We calculated the weighted standardized mean difference (SMD) in

serum vaspin levels between the CAD and control groups.

Results: Our search strategy yielded 36 articles and we included 5 studies enrolling 2236

participants. The median age of the CAD group was 64.5 yrs. (IQR 64-66) compared to 62yrs (IQR

61-63) in the control group. The median body mass index in the CAD group was 25 kg/m2 (IQR

24 – 27) compared to 25 kg/m2 (IQR 24 - 29) in the control group. The unweighted median serum

vaspin levels in the CAD group were 0.69 ng/ml (IQR 0.47 - 0.71) compared to 1.6 ng/ml (IQR

1.6 – 1.9) in the control group. The SMD of serum vaspin level was -0.829 (95% CI -1.013,-0.645)

p<0.001 comparing those in the CAD group and control group.

Conclusion: Serum vaspin levels are significantly and negatively associated with CAD. Current

findings warrant the need to further investigate the role of vaspin in the development of CAD and

its potential to predict incident CAD events.

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084

GEOGRAPHIC VARIATION OF CARDIOVASCULAR DISEASE MORTALITY IN

ASIAN AMERICAN SUBGROUPS J. Pu1, K.G. Hastings2, D. Boothroyd2, P.O. Jose1, S. Chung1, M.R. Cullen2,

L.P. Palaniappan2, D.H. Rehkopf3

1. Palo Alto Medical Foundation, Palo Alto, CA, USA

2. Stanford University School of Medicine, Stanford, CA, USA

Background: Geographic variation in Black/white disparities in cardiovascular disease (CVD)

morality in the U.S. has been documented. However, it remains unknown whether similar

geographic variation in CVD mortality may exist among Asian American subgroups.

Objective: This study examines geographic differences in CVD mortality rates among Asian

American subgroups living in the U.S.

Methods: Age-adjusted CVD mortality rates per 100,000 population and standardized mortality

ratios (SMRs) were calculated for the six largest Asian-American subgroups (Asian Indian,

Chinese, Filipino, Japanese, Korean, and Vietnamese) compared to non-Hispanic whites (NHWs),

using U.S. death records from 2003-2011 and interpolated counts from 2000 and 2010 U.S.

Census data (n=104,223 CVD deaths). States with 100 or more deaths for the specific Asian

American subgroup were included in the analysis.

Results: Among the Asian subgroups, Filipino males in Hawaii (270.5 per 100,000, 95% CI: 259.8-

281.7) and females in Oklahoma (232.3 per 100,000, 95% CI: 152.9-345.6) had the highest age-

adjusted CVD mortality rates. When compared to NHWs, all Asian subgroups had lower CVD

mortality rates in the majority of states. However, higher CVD mortality rates relative to NHWs

were consistently observed across Asian subgroups in Arizona and Nevada. This difference was

largest for Asian Indian males (SMR: 3.2) and females (SMR: 3.7) in Arizona compared to their

NHW counterparts from the same state.

Conclusions: Geographic and racial/ethnic disparities for CVD mortality were present among

certain Asian American subgroups, particularly Filipinos and Asian Indians concentrated in the

Southwest states. Tailored prevention and intervention efforts should be provided to the

populations and geographic areas with higher CVD burden.

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085

MAJOR CAUSES OF DEATH FOR EAST ASIAN SUBGROUPS IN THE UNITED

STATES COMPARED TO COUNTRIES OF ORIGIN (2003-2011) K.G. Hastings1, K.I. Kapphahn1, H. Hedlin1, B. Zhao2, M.R. Cullen1, M. Barry1,

L.P. Palaniappan1, K. Eggleston3

1. Stanford University School of Medicine, Stanford, CA, USA

2. Palo Alto Medical Foundation Research Institute, Palo Alto, CA, USA

3. Stanford University, Shorenstein Asia-Pacific Research Center, Stanford, CA, USA

Background: As populations migrate, evidence shows that disease risks can become more

pronounced or attenuated depending on context and self-selection into migration. While Asian

Americans are typically considered the “healthy minority”, very little is known about their

mortality burden relative to Asian countries of origin and by nativity.

Objective: This study reports the major causes of death among East Asian subgroups in

comparison to respective countries of origin (with Hong Kong as a proxy for high-income Chinese

in Asia).

Methods: We examined U.S. mortality records for Chinese, Japanese, and Korean decedents from

2003-2011 and ranked the major causes of death. Age-adjusted mortality rates were calculated by

age groups and standardized to WHO 2000 standard population. Proportionate mortality (PM)

was calculated for each cause of death by Asian subgroup and nativity status (foreign-born vs.

U.S. born). Data for countries of origin come from the WHO Mortality Database.

Findings: Cancer was the leading cause of death for all groups except for Japanese men in the U.S.

Consistent with later epidemiologic transition in Asia and the “healthy migrant effect”, all-cause

mortality rates were higher in countries of origin than in the U.S (40% and 70% higher in Hong

Kong, 5% and 38% in Japan, and 58% and 113% in Republic of Korea for women and men,

respectively). Cause-specific mortality rates were also higher in countries of origin; however,

Asian subgroups in the U.S. experienced greater PM due to the leading causes of death, especially

heart disease, reflecting in part fewer competing risks. PM of heart disease increased with

proportion born in the U.S.

Conclusion: Our findings highlight differences in mortality between East Asian American

subgroups and countries of origin. More research would help to understand how childhood

exposures, socioeconomic status, self-selected migration, and acculturation interact to explain

these differences.

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98


NEW DIRECTIONS IN CARDIOVASCULAR SURGERY: HEART VALVE SURGERY / CORONARY REVASCULARIZATION / MECHANICAL CIRCULATORY SUPPORT / CARDIAC TRANSPLANTATION

086

TREATMENT OF OBSTRUCTIVE THROMBOSED PROSTHETIC HEART VALVE S.H. Rahimtoola, G. Huang

University of Southern California, Los Angeles, CA, USA

A systematic review of the literature from 1996 -2012 revealed 9 studies with 48 patients with

tricuspid OT PHV in whom thrombolytic therapy was successful in 88%. For left sided OT PHV,

17 studies comprising 756 patients had received thrombolytic therapy (TT) and in 13 studies

comprising 662 patients had received surgical therapy (ST). Females were present 59% (TT) and

66% (ST). All but 3 patients had a mechanical valve. In 10 ST comprising 518 patients, thrombus

was present in 41%, pannus in 38%, thrombus + pannus in 21%. Anticoagulants were described

as inadequate in 39%. Mitral valve was involved in 68% (TT), 73% (ST); remainder had aortic

valve; NYHA Class III/IV 65% (TT) 81% (ST); remainder were in NYHA Class I/II. Recurrence

rate was 13% (TT) 6% (ST); CVA/Emboli 14% (TT) 6% (ST). In TT, complete success was 70%.

30 day mortality was 8%. In (TT) failure rate was 30% with mortality up to 28%. In TT Failure

group, 15 patients died while waiting for surgery. In ST, complete success occurred in 100% with

30 day mortality of 15%. Suggested therapeutic strategies: Tricuspid OT PHV Thrombolytic TT

is first choice. Left sided OT PHV: TT first choice in NYHA FCI/II, those with very severe co-

morbid conditions, ST not a viable option or patient refuses surgery. Left sided OT PHV: ST is

first choice if prosthesis replacement is necessary or appropriate, coronary flow is compromised

TT is contraindicated, pannus is a significant contributor, TT fails.

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087

LEFT ATRIAL APPENDAGE – A NOVEL TECHNIQUE FOR EXCLUSION S.K. Singh, V. Devenraj, D. Kaushal

King George's Medical University, Lucknow, India

Objective: Left atrial appendage ( LAA ) is a frequent site of clot formation in patients with mitral

valve disease, especially in those with atrial fibrillation. Ligation of LAA is commonly performed

during mitral valve surgery. A number of surgical techniques are available for LAA exclusion, but

a failure rate is nearly 60 %. We present here a novel technique to exclude the LAA during mitral

valve surgery. Completeness of LAA ligation was 100 % with this technique which was confirmed

by transesophageal echocardiography ( TEE ) in the follow up.

Methods: We used this technique in 24 patients with rheumatic mitral valve disease with atrial

fibrillation / LAA thrombus who underwent mitral valve replacement over a period of

approximately six months. We used fresh autologous pericardium of appropriate size to close LAA

orifice using 4-0 polypropylene sutures in a continuous manner (Figure 1). In the follow up after

3 months TEE was done in all patients. A history of thromboembolic phenomenon after surgery

was also recorded,

Results: None of the patient presented with any thromboembolic phenomenon in the follow up.

Transesophageal echocardiography after 3 months showed no residual connection between the LA

and LAA. LA clot was present in none of the patients and complete LAA obliteration was observed

in all the patients.

Conclusions: Using an autologous pericardial patch to exclude the LAA, appears feasible with a

low risk of distortion, injury, thrombus migration and incomplete exclusion.

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088

WHICH STEM CELL TYPE IS MORE EFFICIENT AS AN ADJUNCTIVE TO

SURGICAL TREATMENT OF SEVERE ISCHEMIC HEART FAILURE; EXPANDED

MESENCHYMAL OR RECYCLING STEM CELLS? S.H. Ahmadi, M. Soleymani, M. Sahebjam, A.A. Karimi, M. Madani Civi

1. Tehran Heart Center, TUMS, Tehran, Iran

2. Research Dept, Central Hospital; National Iranian Oil Company, Tehran, Iran

Objective: Bone marrow mesenchymal stem cells (MSCs) are used for the treatment of cardiac

disorders. Recycling stem cells (RSC) are a marrow stromal cells with rapid self-renewal capacity

and multipotential differentiation. In a prospective randomized controlled study, we compared 36-

month follow-up results of intramyocardial injection of MSC and RSC on cardiac function in

patients with severe ischemic heart failure undergoing CABG.

Methods: 27 patients with severe ischemic cardiomyopathy were randomly allocated into three

groups; in control group, patients underwent CABG alone whereas in MSC and RSC groups, stem

cells were injected in the border zone of the infarcted myocardium, respectively.

Results: There were no morbidities or mortalities in any of the groups in the study period. In

dobutamine stress echocardiography, the LVEF in MSC group improved significantly (+6.1%)

compared to control (-0.95%) and RS (+1.43%) groups (p<0.05). The wall motion score index of

LAD territories improved in MSC group only, although the differences among the groups were

not statistically significant (-0.18 in control group, -0.27 in MSC group, 0.00 in RS group; p>0.05).

Conclusions: Despite potential abilities of recycling stem cells in proliferation and differentiation,

it seems that intramyocardial injection of MSCs is more efficient than RSC on improvement of

cardiac function as an adjunctive treatment in patients undergoing CABG.

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089

EXAMINING THE COMPLEMENTARY EFFECTIVENESS OF THE ADDITION OF

WARFARIN TO ASPIRIN ON PREVENTION OF SAPHENOUS VEIN GRAFT

THROMBOSIS D. De Leon1, F. Alemu1, M. Bentley1, J. Payne2, T. Ball1

1. Carillon Clinic-Virginia Tech School of Medicine, Roanoke, USA

2. University of Arkansas, Little Rock, Arkansas

Objective: To determine if the addition of warfarin to aspirin prevents SVG thrombosis within 1

year of surgery.

Background: Coronary artery bypass grafting (CABG) is known to improve patient survival and

alleviate symptoms of angina. Saphenous vein graft (SVG) thrombosis, a major cause of morbidity

and mortality is seen in 15-45% of implanted grafts within the first year.

Methods: A retrospective analysis of patients who underwent CABG and repeat coronary

angiography within one year of surgery at Carilion Roanoke Memorial Hospital between 2005 and

2012. Subjects were stratified into two groups, aspirin or aspirin+warfarin, based on the

medications administered at the time of discharge. Surgical and cardiac catheterization reports

were reviewed. Sample size at 95 % confidence interval was calculated for the aspirin group to be

50 patients which was then used for the comparison for the rate graft thrombosis.

Results: 3390 patients in the aspirin group and 385 patients in the aspirin+warfarin group were

identified. Symptom driven repeat coronary angiography was performed in 10.7% (364) of patients

treated with aspirin only while 3.6% (14 p=0.0001) of patients in the aspirin+warfarin group

underwent the same procedure. In the aspirin group (N:50) there were 99 SVG implants and of

those 55 thrombosed (56%). In the aspirin+warfarin (N:15) group there were 50 SVG’s implanted

and of those 9 thrombosed (44 % p=0.02). Conclusion: The addition of warfarin to aspirin therapy

decreases the incidence of Saphenous thrombosis and symptom driven repeat coronary

angiography within 1 year.

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090

RISK FACTORS FOR AAA IN SUBJECTS LESS THAN 65 YEARS OF AGE A. Parashar1,2 , K. Joshi2, V. Chilakapati2 , N. Jarmukli1,2

1. Veterans Affairs Medical Center, Salem, VA, USA

2. VT Carilion SOM, Roanoke, VA, USA

Background: The estimated prevalence of abdominal aortic aneurysm (AAA) is 4 to 9 percent,

which increases with age. Rupture is a potentially catastrophic complication of undiagnosed AAA.

Current United States preventive services task force guideline recommends screening of men who

are ages 65 to 75 and who have ever smoked.

Methods: Data was reviewed on subjects (n=99) who underwent AAA repair at Salem VAMC

from 1998 - 2012. Out of 99- patients with AAA, 36 (36%) were diagnosed with AAA prior to the

age of 65-years and 29 out of 36 (80%) required surgery prior to the age of 65. Demographics/ risk

factors of this subgroup were reviewed. Male gender, tobacco abuse (past or active), Hypertension

were almost universal. 13 out of 36 (36 %) patients were known to have history of CAD, MI,

PCI/CABG. 12 out of 36 (33 %) patients were noted to have peripheral artery disease (PAD). 22

out of 36 (61%) subjects had either CAD/PAD or revascularization (PCI/CABG).MACE

(TIA/CVA, MI, and Death) was noted at day 7 and day 30, only one patient had an event who

developed an MI the day of surgery and died subsequently on day 17 after surgery.

Conclusions:

*A significant number of subjects (36%) were diagnosed with AAA before 65 years of age and

required surgery.

*61% of patients from this younger cohort had evidence of atherosclerotic vascular disease noted

elsewhere (CAD, PAD).

*Clinicians should have a high index of suspicion and consider ultrasound screening for AAA in

similar high risk subjects even if they do not meet current USPTF guidelines.

22

14

AAA < 65 years

CAD/PAD

Without known ASVD

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091

IMPELLA 2.5: TIME FOR A MORATORIUM? P. Samani, R. Arcenas, H. Khattak, H. Hahn, B. Schwartz

Kettering Medical Center, Kettering, Ohio, USA

Background: Cardiogenic shock (CS) in a patient with acute myocardial infarction (AMI) portends

a poor prognosis with mortality rate of 51-76% despite the use of Intra-aortic balloon pump or

Impella 2.5 for hemodynamic support. In the current study, we describe our real world experience

with Impella 2.5 at Kettering Medical Center (KMC) a large community teaching hospital.

Methods: 25 consecutive patients who received Impella 2.5 devices at KMC from May 2011 to

January 2014 was reviewed. The primary end-point was 30-day mortality.

Results: The average age was 70.5 + 12.19 years. Baseline data showed they were all Caucasians,

mostly males (78%) with co-morbidities of: prior AMI (43%), hypertension (80%), diabetes

(78%), chronic kidney disease (33%), and prior stroke (21%). The mean systolic blood pressure

before and after Impella 2.5 placement was 89.64 mmHg + 27.3 and 105.54 mmHg + 16.59

respectively. The overall mortality was 71% with all deaths occurring within five days of Impella

2.5 placement (mean of 2.5 days + 1.64). Multivariate analysis using logistic regression model did

not show any significant difference in mortality based on factors specified for the secondary

endpoints.

Conclusions: The real world 30-day mortality rate in patients with CS in the setting of AMI

remains high despite use of Impella 2.5. This taken together with previously published data calls

into question the utility of Impella 2.5 devices in the setting of CS. If circulatory support is needed

Impella 5.0 or Ventricular assist device should be considered before the Impella 2.5 device.

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092

EXAMINING THE EFFECTIVENESS OF DUAL ANTIPLATELET THERAPY WITH

ASPIRIN AND CLOPIDOGREL IN PREVENTING SAPHENOUS VEIN GRAFT

THROMBOSIS GIVEN ITS PROVEN BENEFIT WITH CORONARY THROMBOSIS D. De Leon1, F. Alemu1, J. Payne2, M. Bentley1, T. Ball1

1. Carillon Clinic-Virginia Tech School of Medicine, Roanoke, USA

2. University of Arkansas, Little Rock, Arkansas, USA

Objective: To determine if the addition of clopidogrel to aspirin prevents SVG thrombosis within

1 year of surgery.

Background: Coronary artery bypass grafting (CABG) is known to improve patient survival and

alleviate symptoms of angina. Saphenous vein graft (SVG) thrombosis, a major cause of morbidity

and mortality is seen in 15-45% of implanted grafts within the first year.

Methods: A retrospective analysis of patients who underwent CABG and repeat coronary

angiography within one year of surgery at Carilion Roanoke Memorial Hospital between 2005 and

2012. Subjects were stratified into two groups, aspirin or aspirin+clopidogrel, based on the

antiplatelet agent(s) administered at the time of discharge. Surgical and cardiac catheterization

reports were reviewed. Sample size at 95 % confidence interval was calculated for the aspirin

group to be 50 patients which was then used for the comparison for the rate graft thrombosis.

Results: 3390 patients in the aspirin group and 605 patients in the aspirin+clopidogrel group were

identified. Symptom driven repeat coronary angiography was performed in 10.7% (364) of patients

treated with aspirin only while 4.5% (27 p=0.0001) of patients in the aspirin+clopidogrel group

underwent the same procedure. In the aspirin group (N:50) there were 99 SVG implants and of

those 55 thrombosed (56%). In the aspirin+clopidogrel (N:27) group there were 50 SVG’s

implanted and of those 22 thrombosed (44 % p=0.18).

Conclusion: The addition of clopidogrel to aspirin therapy in patients undergoing CABG using a

SVG decreases the incidence of early thrombosis and symptom driven repeat coronary

angiography within 1 year of implant.

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CELLULAR AND MOLECULAR MECHANISMS OF CARDIOPROTECTION, CARDIAC REGENERATION AND REMODELING

093

INFLAMMATION IN HEART DISEASES

D.K. Singla

University of Central Florida, Orlando, FL, USA

The main objective of this study was to determine whether or not inflammation plays a role in

heart diseases. We will demonstrate presence of inflammation in pre-diabetic (PD)

cardiomyopathy and diabetic infarcted heart. We will define the role of monocytes and their

differentiation into pro-inflammatory M1 and anti-inflammatory M2 macrophages. In PD

cardiomyopathy model our data suggest that there was a significantly increased infiltrated

monocytes and associated pro-inflammatory cytokines that induces adverse cardiac remodeling,

and heart dysfunction in the PD group. Following BMP-7 treatment in PD cardiomyopathy group

we observed increase in M2 macrophage polarization that are associated with an increase in anti-

inflammatory cytokines. Enhanced anti-inflammatory cytokines reduced adverse cardiac

remodeling, and improved cardiac function in the PD+BMP-7 group. In conclusion, our data

suggest, that diabetic cardiomyopathy is associated with increased monocyte infiltration, released

of pro-inflammatory cytokines, which contributes to adverse cardiac remodeling, and cardiac

dysfunction.

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094

C-REACTIVE PROTEIN MODULATION OF INFLAMMATION IN ACUTE

CORONARY ARTERY DISEASE

J.G. Filep

University of Montreal, Montreal, QC, Canada

C-reactive protein (CRP) is an acute-phase reactant and an active regulator of innate immunity.

Clinical studies have shown that elevated baseline serum CRP levels confer, albeit to varying

degrees, additional prognostic value for future coronary artery disease (CAD) and death and may

be useful for risk-guided therapy. CRP has been implicated in multiple aspects of atherogenesis

and acute CAD; however, whether CRP plays a direct causal role in these events remains

controversial. Studies in rodents yielded conflicting results on atherosclerosis development. CRP

has at least two conformationally distinct forms, native pentameric (p) CRP and monomeric

(m)CRP. Loss of pentameric symmetry in pCRP, yielding mCRP, is associated with expression of

distinct bioactivities. Using CRP isomer-selective antibodies, we detected mCRP, but not native

CRP in human coronary artery atherosclerotic lesions with more pronounced mCRP staining in

advanced fibro-fatty plaques than fatty streak lesions. The mCRP staining frequently co-localized

with neutrophils and macrophages in advanced lesions. In vitro, mCRP is considerably more potent

activator of human coronary artery endothelial cells and monocytes than pCRP, whereas mCRP

and pCRP exert opposing actions on neutrophil trafficking and apoptosis through distinct Fc-

gamma receptors and lipid rafts. Unlike pCRP, mCRP is susceptible for proteolysis, resulting in

peptide 201-206 that exhibits potent anti-inflammatory and anti-platelet activities. These findings

may explain how sequential conformational changes in CRP’s structure could lead to expression

of distinct biological activities that may modulate inflammation underlying plaque destabilization

and acute CAD.

(Grant support: CIHR).

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095

CARDIOPROTECTIVE EFFECTS OF THERAPEUTIC T3 TREATMENT IN

MYOCARDIAL INFARCTION AND ISCHEMIA REPERFUSION

A.M. Gerdes, V. Rajagopalan, Y. Zhang, Y. Chen

Department of Biomedical Sciences, New York Institute of Technology-College of Osteopathic

Medicine, Old Westbury, USA

Background: Myocardial Infarction (MI) leads to cardiac tissue hypothyroidism, a condition that

by itself can lead to heart failure (HF). Potential improvements in LV remodeling and function

with a therapeutic T3 dose after MI and ischemia/reperfusion (IR) are not clear.

Objectives: We hypothesize that a safe, low-dose T3 treatment/monitoring regimen will lead to

significant cardioprotection in rats following MI and 60 minute IR.

Methods: MI was produced in adult rats by LAD ligation. T3 (4-5 μg/kg/day) in drinking water

was started after MI and continued for 2 months (Mo). Vehicle (V) was used in MI controls (n=16-

20/group). The same 2 month treatment protocol was used for rats with IR.

Results: Infarct size was similar in MI and MI+T3 groups. D3 mRNA expression increased in

MI+V (2.7-fold) and was reversed in MI+T3 (0.49-fold). MI+T3 improved ejection fraction by

51% at 1 Mo and by 47% at 2 Mo post-MI as assessed by magnetic resonance imaging (MRI).

Mean MRI wall thickness was increased at both latter time-points. Histologically, non-infarct area

and wall thickness increased significantly (30% and 18% respectively). Non-infarct length was

also increased. Remarkably, following MI, the incidence of atrial tachyarrhythmias that persisted

following discontinuation of experimental atrial tachypacing was significantly diminished by 63%

with T3. T3 did not affect heart rate. The T3 dose led to feedback inhibition of Thyroid-Stimulating

Hormone (TSH) but no significant change in serum T3. T3 treatment for 2 months after IR also

led to an increase in viable myocardium and improvement in LF function.

Conclusion: Results demonstrate a safe and effective post-MI and IR T3 treatment strategy that

dramatically improves LV function, atrial arrhythmogenesis, non-infarct tissue remodeling, and

myocyte survival with no adverse effects. This study describes an effective, translatable,

treatment/monitoring protocol for T3 treatment of MI and IR.

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096

REGULATION OF INTESTINAL GENES BY AN ORAL PEPTIDE REDUCES

SYSTEMIC INFLAMMATION AND ATHEROGENESIS

M. Navab, S. Mottahedan, G. Doroudian, A. Parsa, F. Yazdanpanah, M. Sharifzadeh,

S. Vazirian

David Geffen School of Medicine, University of California, Los Angeles, CA, USA

A high fat, high cholesterol diet (Western diet, WD) increases the levels of the potent growth

promoter unsaturated lysophosphatidic acid (LPA) in small intestine and plasma of LDLR-/- mice.

Supplementing mouse chow with unsaturated LPA produced dyslipidemia and inflammation. WD

increased the expression of the genes Acadl, Acot1 and Angptl4 while reducing that of Reg3g. The

transgenic plant reversed the changes in gene expression. We now report that supplementing chow

with unsaturated LPA resulted in aortic atherosclerosis, which was ameliorated by adding a

transgenic 6F plant powder. Supplementing chow with lysophosphatidylcholine (LysoPC) 18:1

resulted in dyslipidemia similar to that seen on adding LPA 18:1 to chow. A specific inhibitor of

autotaxin (PF8380) significantly ameliorated the dyslipidemia induced by LysoPC 18:1.

Supplementing chow with LysoPC 18:1 markedly increased the levels of unsaturated LPA in small

intestine, plasma and liver. This increase was ameliorated by PF8380 indicating an autotaxin-

dependent conversion of LysoPC 18:1 to LPA 18:1. Adding LysoPC 18:0 to chow increased levels

of LPA 18:0 in small intestine, plasma and liver. This was not altered by PF8380 indicating that

conversion of LysoPC 18:0 to LPA 18:0 was not autotaxin-dependent. We therefore conclude that

a) autotaxin mediates the conversion of unsaturated LysoPC to LPA, and b) intestinally-derived

unsaturated LPA can cause atherosclerosis in LDLR-/- mice.

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097

ALTERATIONS OF MACROPHAGE GSH/GSSG STATUS REGULATE CD36

EXPRESSION AND FOAM CELL FORMATION: IMPLICATION OF GSH-

ANTIOXIDANT SYSTEM IN ATHEROSCLEROSIS X. Yang, H. Yao, Y. Chen, Y. Duan, J. Han

Nankai University, Tianjin, China

The glutathione (GSH)-dependent antioxidant system has demonstrated to inhibit atherosclerosis.

Macrophage CD36 uptakes oxidized low-density lipoprotein (oxLDL) thereby facilitating foam

cell formation and development of atherosclerosis. It remains unknown if GSH can influence

macrophage CD36 expression and foam cell formations. Herein, we report that treatment of

macrophages with L-buthionine-S,R-sulfoximine (BSO) decreased the cellular GSH production

and ratio of GSH to glutathione disulfide (GSH/GSSG) while increasing production of reactive

oxygen species. Associated with decreased GSH levels, macrophage CD36 expression was

increased which resulted in foam cell formation. In contrast, N-acetyl cysteine and antioxidant

enzymes (catalase and superoxide dismutase) blocked BSO-induced CD36 expression and foam

cell formation. In vivo, administration of mice with BSO increased CD36 expression in peritoneal

macrophages and kidneys. BSO had no effect on CD36 mRNA expression and promoter activity

but still activated CD36 protein expression in macrophages lacking PPARgamma expression

suggesting it induced CD36 expression at the translational level. Indeed, we determined that BSO

enhanced CD36 translational efficiency. Taken together, our study demonstrates that cellular GSH

levels and GSH/GSSG status can regulate macrophage CD36 expression and foam cell formation,

and further supports the important role of the GSH-antioxidant system in anti-atherosclerosis by

providing molecular and cellular evidence.

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098

RELAXIN, A POTENTIAL THERAPY FOR ATRIAL FIBRILLATION B. Henry, C. McTiernan, A. Parikh, D. Patel, S. Shroff, D. Schwartzman, G. Salama

University of Pittsburgh, Pittsburgh, PA, USA

Relaxin, a hormone of reproduction and has been identified as an insulin-like peptide with

pleiotropic actions throughout the body including important cardiovascular actions. We recently

demonstrated that Relaxin suppresses atrial fibrillation (AF) in spontaneously hypertensive rat

(SHR) hearts by remodeling the extracellular matrix, modulating cardiac ion channels and

reducing cell hypertrophy. Here, we test the potential therapeutic effects of Relaxin in a geriatric

model of AF based on old rats (F-344, 24-months). Rats were implanted with osmotic mini-pumps

(Alzet) to deliver Relaxin for 2-weeks (0.4 mg/kg/day) or to deliver the vehicle as controls. Heart

rate, blood pressure and serum relaxin were measured at the onset and at the end of the 2-weeks

treatment. Hearts were perfused in a Langendorff apparatus to optically map action potentials and

Ca2+ transients, conduction velocity (CV), restitution kinetics, programmed stimulation (10-S1-

S1 impulses at 300 ms CL, decreasing S1-S2 intervals) was applied to assess AF susceptibility,

then atrial tissues were prepared for analysis by immuno-cytochemistry and RT-PCR. In control

hearts, sustained AF was readily elicited (n=7/8) whereas AF was suppressed in relaxin treated

rats (n=0/8). Relaxin increased CV by ~2-fold, reversed fibrosis and cellular hypertrophy.

Consistent with these cardiac effects, collagen (I&III) deposition was reduced as well as transcripts

of fibrosis (TGF-beta, collagen I and III, metalloproteinase 1 and 9) and upregulated voltage-gated

Na+ channels Nav1.5 protein by 1.8 fold compared to untreated old-rats. In whole cell voltage-

clamp experiments, atrial myocytes incubated with 100 nM relaxin for 24-48 hours had a 2-fold

increase in current density compared to myocytes incubated with vehicle. These results may

explain the clinical trial results of greater survival (37%) of patients with acute heart failure whom

received relaxin (2-days,i.v.) and suggest that Relaxin may be a transformative therapy for AF.

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CHRONIC ISCHEMIC HEART DISEASE – MECHANISMS AND MANAGEMENT

099

IMPACT OF PERCUTANEOUS INTERVENTION OF CORONARY CHRONIC TOTAL

OCCLUSION ON LEFT VENTRICULAR EJECTION FRACTION Y.R. Manda, S. Agrawal, R. Durkin, C. Sarnoski, P. Puleo, J. Shirani

St Lukes University Health Network, Bethlehem, PA, USA

Background: Percutaneous coronary intervention (PCI) of coronary artery chronic total occlusion

(CTO) has been gaining popularity with reported high success rates in these anatomically complex

and challenging lesions. However, changes in left ventricular ejection fraction (LVEF) associated

with successful PCI have not been well studied.

Methods: We performed a systemic review of the literature and identified 14 prospective and 2

retrospective studies that specifically addressed this issue. Meta-analysis was performed to

compare the changes in left ventricular EF associated with successful versus unsuccessful PCI.

Results: A total of 615 patients were included in this meta-analysis from 16 studies. Mean age of

study patients was 60.5 years and 81% were men. Median duration of follow up was 6 months

(range 1 to 36). LVEF was measured by invasive angiography (3 studies), cardiac magnetic

resonance imaging (7 studies) and two-dimensional echocardiography (6 studies). Mean

improvement in ejection fraction was 4.09% (95% confidence interval 2.91 to 5.28; p<0.00001) in

those with successful PCI of CTO lesions [Figure]. An improvement in systolic wall thickening in

CTO territory was also observed in 3 studies (p<0.001).

Conclusion: Successful PCI of coronary artery CTO improves LVEF and systolic wall thickening

in selected patients.

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100

UTILITY OF A NOVEL CORONARY ARTERY DISEASE BIOMARKER

ALGORITHM IN MODIFYING PHYSICIAN ADHERENCE TO GUIDELINE-BASED

THERAPY D.S. Harrington1, N.D. Wong2, Y. Luo3

1. University of Southern California, Los Angeles, USA

2. University of California, Irvine, CA, USA

3. UCLA, Los Angeles, CA, USA

Background: Initial coronary artery disease (CAD) presentation for most patients is acute coronary

syndrome (ACS) from rupture of non-obstructive plaque. Screening for ACS risk remains a

challenge; traditional risk factors and standard noninvasive testing predict only 60-65% of events.

In this study, we examined whether providing physicians with a novel CAD predictive algorithm

would impact their management of patients to conform more appropriately to established

guidelines.

Methods: We studied 22 physician practices including cardiology, internal medicine, family

practice, obstetrics and gynecology, and endocrinology. Participating physicians developed a

treatment plan per their usual standard of care. In patients at intermediate risk based on established

risk factors, a novel CAD predictive algorithm (CADPA) using biomarkers (CTACK, Eotaxin, Fas

Ligand, HGF, IL-16, MCP-3, sFas, Hba1c, HDL-C) and key risk factors (age, sex, diabetes, and

family history) was then applied, providing revised CAD risk estimates (low <3.5%, intermediate

3.5-7.49%, and high >7.49% CAD risk in 5 years). Physicians then had the opportunity to revise

their treatment plan. All treatment plans were documented and recorded by an independent trial

monitor.

Results: A total of 583 patients were evaluated using traditional risk assessment and 144 (25%)

were initially classified as intermediate risk; 10 patients were lost to follow-up. The remaining 134

intermediate-risk patients (mean age 61.6 years, 36% female), based on CADPA results, were

reclassified as low (8.2%), intermediate (30.6%), or high (61.2%) risk and new treatment plans

were developed at the discretion of the treating physicians. Lifestyle or drug treatment plans were

changed in 57% of the cases (P<0.001), conforming more appropriately to ATPIII/AHA guidelines

(85%). Most physicians (96%) agreed that CADPA provided information that would impact their

current treatment decisions.

Conclusion: Implementation of a novel CAD predictive algorithm provides additional actionable

clinical information that results in more appropriate therapy and alignment with current guidelines.

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101

CYP2D6 GENETIC INFORMATION-GUIDED METOPROLOL USE IN A

CARDIOLOGY CLINIC – A PROSPECTIVE STUDY A. Kodali1, K. Khalighu1, Y. Wu1, S.A. Mirabbasi1, B. Khalighi2, W.Q. Fan1

1. Easton Hospital, Easton, PA, USA

2. Temple University, School of Pharmacy, Philadelphia, PA, USA

Background: The CYP2D6 enzyme is a major determinant of metoprolol plasma clearance. It has

close to 100 genetic polymorphisms, which give rise to four phenotypic: Extensive-Metabolizers

(EM, normal capacity), Intermediate-Metabolizers (IM, reduced capacity), Poor-Metabolizers

(PM, diminished capacity) and Ultra-extensive-Metabolizers (UM, higher than average capacity).

Peak plasma metoprolol concentrations can be 2.1-4.6 fold greater in the IM/PM groups as

compared with the EM group.

Objectives: To evaluate CYP2D6 genetic variations in patients and assess the clinical outcomes of

this genetic information-guided metoprolol dosing.

Methods: DNA sequences of CYP2D6 are analyzed in 479 patients. Individual metoprolol

recommendations are made based on their phenotype and are then followed up at the clinic.

Results: Distribution of CYP2D6 phenotypes in our patients are (expressed as phenotype: patient

number): EM: 251, IM: 158, PM: 64 and UM: 6. Distribution of the 306 (63.8%) patients who are

on metoprolol are: EM: 159, IM: 102, PM: 39 and UM: 6. Metoprolol was decreased in dose in 26

patients and switched to atenolol in 125 patients. Dose is unchanged in 192 patients who are either

already on a low dose or tolerating current dose. Doses are increased in UM patients. For those

who’re not on metoprolol but phenotypically abnormal (IM: 59 and PM: 25), “metoprolol caution”

is documented. All patients are then followed up for one year with primary endpoints of 1) ACS-

or-CHF-related hospitalization, 2) cardiac death and 3) symptomatic bradycardia, hypotension or

syncope.

Conclusions/Discussion: Metoprolol should be used with caution in patients with CYP2D6

variants due to the marked pharmacokinetics effect. Prevalence of IM, PM and RM phenotypes

are substantial (combined 48%). Lowing dose or switching to beta-blocker that is not metabolized

by CYP2D6 in IM/PM patient should decrease major side effects, whereas increasing dose in RM

patients should increase clinical efficacy.

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102

SERUM CYSTATIN C, AN INDEX OF RENAL DYSFUNCTION, AS A MARKER IN

ISCHEMIC HEART DISEASE M.M. Gevorgyan1, N.P. Voronina1, T.V. Kozaruk1, Ts.P Korolenko2, T.A. Korolenko2

1. Scientific Center of Experimental and Clinical Medicine, SB RAMS, Novosibirsk, Russia

2. Institute of Physiology and Fundamental Medicine SB RAMS; Novosibirsk, Russia

Objectives. To investigate whether patients with ischemic heart disease display altered serum

cystatin C as a possible biomarker of acute ischemia.

Background. Cystatin C, a well-known index of renal dysfunction, more efficient than creatinine,

was recently suggested as a candidate biomarker in cardiovascular pathology. However, the

precise role of cystatin C in acute ischemia and myocardial infarction is not studied enough. The

aim: to evaluate serum cystatin C in patients with ischemic heart disease in dynamics of myocardial

infarction development.

Methods. 42 male patients (62 ± 5.0 years) were enrolled in a study; the control group consisted

of 60 healthy persons of the appropriate age. Serum hs-CRP, D-dimer, cystatin C, creatinine, urea,

lipid profile, LDH, CPK, CPK-MB were measured with help of Architect 8000 (Abbott, USA) and

with Access-2 (Beckman Coulter, USA), pro-BNP by ELISA method.

Results. In healthy persons, aged 50-60, an elevation of serum cystatin C was shown vs healthy

persons, aged 20-40 years. In patients with ischemic heart disease, there was a significant (p <

0.001) increase in serum CPK-MD, hs-CRP, D-dimer and elevated (p < 0.01) CPK, cystatin C vs

the control. Positive correlation was shown between serum pro-BNP and cystatin C (r = 0.57, p<

0.05), pro-BNP and urea (r = 0.49, p< 0.05) indicating on cardio-renal syndrome development.

Conclusions. In patients with myocardial infarction serum pro-BNP, cystatin C were elevated more

significantly as compared with hs-CRP and D-dimer levels, indicating that these indexes can be

used as predictors of increased risk of acute ischemia.

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103

CORONARY SINUS FILLING TIME IN PATIENTS HAVING ANGINA WITH

NORMAL EPICARDIAL CORONARY ARTERIES S.K. Banerjee, M.F.I. Khaled, C.M. Ahmed, T. Parvin, D.K. Adhikary

BSMMU, Shahbag, Dhaka, Bangladesh

Objective: We evaluated Coronary sinus filling time (CSFT) in patients having angina with normal

epicardial coronary arteries and compared it with control population.

Background: Patients having angina with normal epicardial coronary arteries are often considered

to have coronary microvascular dysfunction that results in coronary slow flow. CSFT may

represent transit time through coronary microcirculation.

Method: We enrolled 31 patients having definite angina or probable angina with positive exercise

tolerance test with normal epicardial coronary arteries in coronary angiogram (CAG) in study

group and 31 patients having normal epicardial coronary arteries in CAG during preoperative

evaluation before surgical treatment for valvular and congenital heart diseases in control group.

CSFT, TIMI (Thrombolysis In Myocardial Infarction) frame count, cTIMI (Corrected TIMI) frame

count and TMP (TIMI Myocardial Perfusion) score were assessed in CAG of both groups and

compared between groups.

Results: Patients’ Mean±SD of age in study and control group were 48.84±9.50years and

46.71±5.53years respectively with no significant difference (p=0.569). There was female

preponderance (55% and 65%) in both groups. CSFT was significantly prolonged in study group

(4.22±0.71sec vs. 3.65±0.25sec, P value 0.001) but TIMI frame count, cTIMI and TMP showed

no significant difference between two groups (25.71±5.74 vs. 26.74±3.81, p= 0.552; 14.76±3.6 vs.

15.4±2.56, p=0.449; 2.54±0.5 vs. 2.61±0.49, p=0.326; respectively).

Conclusion: We concluded that CSFT was significantly prolonged in patients having angina with

normal epicardial coronary arteries which might be a surrogate marker for diagnosis for coronary

microvascular disease.

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104

INCREASED LV MASS IS RELATED WITH ATYPICAL CHEST PAIN IN WOMEN M.S. Shin1, Y.H. Kim2, W.J. Shim3, S.M. Park4, K.I. Cho5, M.A. Kim6, G.J. Shin7,

K.S. Hong8 1. Heart Center, Gachon University Gil Medical Center, Korea

2. Cardiovascular Division, Department of Internal Medicine Korea University Ansan Hospital, Korea

3. Cardiovascular Center, Korea University Anam hospital, Korea

4. Cardiovascular Center, Kosin University Gospel hospital, Korea

5. Cardiovascular center, Seoul national university Boramae hospital, Korea

6. Cardiovascular center, Ewha women's university Mokdong hospital, Korea

7. Cardiovascular center, Chuncheon Sacred Heart hospital, Korea

Background: Chest pain in women seems to have different features from that in men with chest

pain. Korean Women’s Registry was established to elucidate unique features of chest pain in

women in 2011. We evaluated demographic characteristics including obstetric history as well as

echocardiographic and coronary angiographic data and treadmill exercise test (TMT).

Methods: 880 women patients with chest pain in Korean Women’s Registry, which is a multicenter

registry, were enrolled. The findings of TMT and echocardiography and clinical data were

analyzed. 197 patients were performed dobutamine stress echocardiography (DSE). Among them,

102 patients were finally enrolled for the DSE analysis according to exclusion criteria.

Results: Patients who showed left ventricular (LV) outflow tract obstruction during DSE have

higher LV mass index and LV relative wall thickness and diastolic dysfunction. Typical angina is

not a good diagnostic indicator of coronary arterial disease (CAD) in women. After age 55, classic

angina classification is moderately predictive of CAD. Patients with positive TMT showed lower

LV mass index and higher pulmonary artery systolic pressure. Conventional predictors of CAD

such as age, DM and hypertension were not different in prevalence between patients with negative

or positive TMT. After multivariate adjustment, significant CAD seems to be only predicted by

duration of TMT, indicator of exercise capacity.

Conclusion: DSE-provoked LV outflow tract obstruction is related to LV concentric remodeling

and LV diastolic dysfunction and may be associated to the limited exercise tolerance in Korean

women with chest pain regardless of coronary artery disease. Duration of TMT was an independent

predictive factor of the presence of CAD by multivariate analysis. Increased LV mass and diastolic

dysfunction were related with atypical chest pain in women.

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105

HEART ATTACKS IN YOUNG ADULTS OF CENTRAL CALIFORNIA O.S. Sandhu, B.K. Joshi

University of San Francisco Fresno, Fresno, CA, USA

Patients admitted over a ten-year time period were included in this case-controlled retrospective

study. Using ICD 9 codes, patients admitted with diagnosis of acute coronary syndrome (ACS),

STEMI and NSTEMI, were identified. Random sample of 100 patients was selected from each of

the four groups (young ACS, old ACS, young non-ACS, and old non-ACS). Young was defined

as between age 18 and 50, while old was defined as 50 and older. Lipid profiles were significantly

different in the comparison groups. Young ACS patients had higher mean TG when compared to

old ACS patients; (P=0.001). Young ACS patients experienced significantly more metabolic

syndrome as defined by TG/HDL ratio greater than 3.5 (P = 0.02). Hypertension was more

prevalent in older ACS patients (71%) followed by older non ACS patients adults (64%)

(P=0.001). History of cardiac disease (41%) was more common in older ACS patients as well

(P=0.024). BMI, race, illicit drug use, and prevalence of diabetes mellitus did not differ

significantly between young and old ACS adults or the non ACS groups. On multivariate logistic

regression analysis, male sex (OR 2.73, 95% CI 1.38-5.39, P=0.001), smoking (OR 2.74, 95% CI

1.47-5.09, P=0.005), and metabolic syndrome (OR 2.91, 95% CI 1.52-5.5, P=0.006) were

independently associated with young patients presenting with ACS. Young ACS adults are more

likely to be males, smokers, and have propensity for single vessel disease, specifically the LAD.

Metabolic syndrome is associated with ACS in young adults, potentially requiring additional risk

stratification and control beyond traditional risk factors.

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ADVANCES IN HEART FAILURE, CARDIOMYOPATHIES AND PULMONARY HYPERTENSION

106

COLCHICINE FOR PREVENTION OF PERICARDITIS RECURRENCE: META-

ANALYSIS OF RANDOMIZED CONTROLLED TRIALS M.S. Salih, H.A. Mlatoum, E. Leung, D.G. Meyers

St Luke's Hospital, Chesterfield, MO, USA

Objectives: To evaluate the efficacy and safety of colchicine use in the treatment of acute

pericarditis and prevention of pericarditis recurrences.

Background: Recurrent pericarditis is the most common complication of acute pericarditis.

Colchicine has been used for several centuries as an anti-inflammatory treatment for arthritis and

acute gout attacks. There have been studies that suggest colchicine as a first-line treatment for

acute pericarditis and for prevention of recurrent episodes. Recently studies have shown that it is

superior to conventional therapy, which includes nonsteroidal anti-inflammatory drugs (NSAIDs).

Methods and results: Electronic databases were searched to identify randomized control trials that

evaluated the effects of colchicine vs. NSAIDs or placebo for treatment of acute or recurrent

pericarditis. The primary endpoint was recurrent pericarditis. The safety end point was any side

effects. Odds ratios (OR) and 95% confidence intervals (CI) computed using fixed-effect model.

Eight randomized controlled trials were included in the meta-analysis, enrolling a total of 1635

patients. Colchicine significantly reduced the rate of recurrent pericarditis (OR 0.382; 95% CI,

0.300-0.486, P = 0.000, NNT = 6, I2 = 0.000) but when compared with conventional treatments,

the risk of side effects were higher with colchicine (OR 1.457, 95% CI, 1.038-2.045, P = 0.029,

NNH = 29, I2 = 0.000)

Conclusions: Colchicine is an effective treatment for acute pericarditis and superior to NSAIDs

for prevention of pericarditis recurrences without a significant risk of serious side effects.

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107

PATTERN OF CARDIAC SURVEILLANCE AMONG LYMPHOMA PATIENTS

RECEIVING ANTHRACYCLINE-BASED CHEMOTHERAPY O.Y. Hung, J.R. Brown, T. Dai, K.A. Easley, C.R. Flowers, S. Parashar

Emory University, Atlanta, GA, USA

Background: Anthracyclines are potent anti-neoplastic agents in the treatment of lymphoid

malignancies but their therapeutic benefit is limited by cardiotoxicity. The American Heart

Association (AHA) recommends routine surveillance, early diagnosis and treatment of

anthracycline-based chemotherapy (AC) induced cardiomyopathy (AC-CMP). We aimed to assess

the prevalence of AC-CMP in lymphoma patients, surveillance patterns of left ventricular ejection

fraction (LVEF) in those receiving AC and management of AC-CMP patients at an academic

medical center prior to the development of a comprehensive cardio-oncology program.

Methods: We performed a retrospective cohort study examining 218 patients with aggressive B-

cell Non-Hodgkin lymphomas (B-NHL) who received AC 1992-2012 and had serial follow-up.

AC-CMP was defined as LVEF decrease >=10% with final LVEF =<50% or LVEF reduction

>=15% regardless of final LVEF.

Results: Of 218 patients treated with AC, 73 (34%) had LVEF assessment both prior to and after

receiving AC. Of these 73 patients, 24 developed AC-CMP and had higher cumulative all-cause

mortality than those without AC-CMP (HR 2.35, p=0.03). Coronary artery disease (CAD) was an

independent predictor of AC-CMP (p=0.048). Mean post-AC LVEF was lower in CAD patients

compared to those without CAD when their baseline LVEF was 45% (p=0.0009) or 55% (p=0.001)

but was similar at 65% (p=0.33). Less than half of AC-CMP patients received recommended heart

failure medication therapy.

Conclusions: Historically, one third of B-NHL patients treated with AC underwent surveillance

according to AHA guidelines. There is substantial opportunity for collaboration between

oncologists and cardiologists to improve the care of lymphoma patients receiving AC.

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108

LEFT VENTRICULAR ASSIST DEVICE (LVAD) REVERSES INHIBITION ON BETA-

ADRENERGIC RECEPTOR RESENSITIZATION E. Martelli, A. Chattterjee, C. Moravec, R. Starling, S.V. Naga Prasad

Cleveland Clinic, Cleveland, OH, USA

Traditionally left ventricular assist device (LVAD) is used for mechanical unloading of the heart

in conditions of chronic heart failure. Post-LVAD there is significant preservation of cardiac

function in part, due to recovery in beta-adrenergic receptor (betaAR) function. BetaAR function

is regulated by phosphorylation (desensitization/shutting off) and dephosphorylation

(resensitization/re-activation) of the receptor. Increased betaAR desensitization is a classical

hallmark of heart failure but not much is known about betaAR resensitization. In order to test

whether resensitization plays a role in recovery of betaAR function post-LVAD, we used pre- and

post-LVAD human heart samples to assess PI3K activity, PP2A activity, beta2AR

phosphorylation and adenylyl cyclase (AC) activity as a measure of G-protein coupling.

Significant PI3Kgamma activity was observed in pre-LVAD samples compared post-LVAD and

non-failing human heart samples. Similarly, AC activity was markedly reduced in pre-LVAD

samples compared to post-LVAD and non-failing showing reduced ability of receptors to couple

to G-proteins indicating reduced recovery of receptor function in post-LVAD heart samples.

Consistent with the reduced recovery in betaAR function in pre-LVAD samples, significant

betaAR phosphorylation was observed in pre-LVAD compared to post-LVAD and non-failing.

Correspondingly, we observed significant reduction in endosomal PP2A activity in the pre-LVAD

samples which was remarkably reversed in post-LVAD samples similar to the activity in non-

failing. These studies suggest that resensitization is inhibited in end-stage human heart failure and

may critically contribute to cardiac remodeling and hypertrophic response upon cardiac stress.

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109

THE IMPACT OF LIVER TRANSPLANTATION ON MYOCARDIAL FUNCTION IN

PATIENTS WITH FAMILIAL AMYLOID POLYNEUROPATHY R. Placido, N. Cortez-Dias, M. Nobre e Menezes, G. Lima da Silva, I. Conceicao,

T. Guimaraes, S. Goncalves, A.G. Almeida, F. Pinto, C. Azevedo Coutinho


Portugal

Introduction: familial amyloid polyneuropathy (FAP) is a genetic disorder characterized by

amyloid deposits in multiple organs. Myocardial amyloid infiltration results in diastolic

dysfunction and subclinical changes in systolic function, better assessed by myocardial

deformation parameters. Liver transplantation (LT) inhibit liver production of abnormal protein

and prevent disease progression. However, its impact on myocardial deformation has never been

assessed.

Objective: To evaluate the impact of LT in global myocardial deformation parameters depicted by

speckle-tracking echocardiography in patients with FAP.

Methods: Prospective study of patients with FAP undergoing LT. Global longitudinal strain (GLS)

and global longitudinal systolic (GLSR-S), protodiastolic (GLSR-E) and end-diastolic (GLSR-A)

strain rate were evaluated prior to surgery and repeated at least 1 year thereafter.

Results: Eighteen patients (66.7% female; 39 ± 7 years) with FAP undergoing LT were included.

At baseline the neurophysiological median score was 5 [Interquartile range (IQR): 0-14]. All

patients had mild neurological symptoms, but none exhibited cardiovascular symptoms. The

severity of neurological involvement correlated with the GLSR-S impairment (Pearson R: 0.49,

P=0.042). Sixty seven percent of patients had significantly improvement of GLS 3.5 years

(median) after LT (post-LT: -18.9 ± 3.0% vs. pre-LT: -17.4 ± 2.4%; p = 0.05). There was

consistency between GLS variation and the improvement of the other deformation parameters

(GLSR-S variation: Pearson r=0.66, P=0.003; GLSR-E variation: Pearson R=-0.55, P=0.019;

GLSR-A variation: Pearson R=-0.55, P=0.017). Variation of myocardial deformation did not

depend on age, duration of symptoms or severity of neurological involvement.

Conclusion: Patients with FAP have subclinical changes in systolic function assessed by

myocardial deformation analysis, which correlates with the neurological involvement of the

disease. After LT, changes in myocardial deformation tend to be reversed.

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110

RESOLUTION OF THE S WAVE IN LEAD I: A CRITERION OF SUCCESSFUL

THROMBOLYSIS IN ACUTE PULMONARY EMBOLISM D.B. Petrov, M.H. Milanova

Emergency Hospital "Pirogov" Sofia, Bulgaria

Objective: To determine whether a simple, readily applicable electrocardiographic (ECG) criterion

such as rapid reduction of the S wave in lead I(SI),will allow early prediction of successful

thrombolysis in patients with acute massive pulmonary embolism(PE).

Background: In contrast to myocardial infarction, there are no strict ECG criteria for assessing the

efficacy of thrombolysis in acute pulmonary embolism.

Methods: Our study enrolled two hundred patients admitted in our Department with the diagnosis

of massive PE (confirmed by computed tomography scan) during a period of thirteen years (from

July 2001 to May 2014). Thrombolysis involved the use of alteplase at a dose of 100 milligram

over a 2-hour period followed by unfractioned heparin as a bridge to anticoagulation with warfarin.

A baseline(pre-thrombolysis)12-lead ECG was recorded immediately before initiation of alteplase

and at 60 minutes,120 minutes and 24 hours thereafter(post-thrombolysis ECG).The ECG marker

studied was the S wave in lead I >1 millimeter. Patients with either contraindication to fibrinolysis

and previously intraventricular conduction defects were excluded from the study.

Results: Two group were created: group A including 136(68%) patients with successful

thrombolysis and group B including 64(32%) subjects with unsuccessful thrombolysis. We

observed a newly emerged deep SI in 114(84%) of the patients in group A and SI was present in

51(80%) of the subjects in group B. Rapid reduction of SI in the post-thrombolysis ECG in the

first 24 hours was detected in 102(90%) of the patients in group A. There was no resolution of the

SI in any of the patients in group B after completion of the fibrinolysis in the first 24 hours.

Conclusions: Resolution of the S wave in lead I can be used as an ECG marker and a simple

bedside tool for predicting of successful reperfusion after thrombolysis in acute pulmonary

embolism.

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111

EXERCISE HEMODYNAMICS AMONG PATIENTS WITH DYSPNEA ON EXERTION

M. Rumbak, J.H. Kim, M. Sadique, M. Ali, A. Qamar, A. Ali

Institute of Cardiovascular Excellence, Ocala, FL, USA

Background: Among patients with shortness of breath, whose echocardiogram suggests pulmonary

arterial hypertension, the next step is a right heart catheterization. Patients symptoms are at

exercise thus, we elect to measure exercise hemodynamics. We present series of patients whose

hemodynamics suggest diastolic dysfunction causing pulmonary venous hypertension on exercise.

Methods: After informed consent, patients had right heart catheterizations and had normal

hemodynamics at rest. We exercised these patients for 3 minutes with a 2.5 pound weight with

repeat hemodynamics. Patients were also subjected to a cardiopulmonary stress test (CPET).

Results:

Mean PA Pressure Patient Number Mean PA pressure with

exercise

Lesser than 25 mm at baseline

(normal)

53 unchanged

Greater than 25 mm at

baseline

30 NA

Lesser than 25 mm at baseline

(normal)

49 increased

(15 of 19 had elevation of

PCWP above 18 mm)

Among 49 patients out of 102 who had normal mean PA pressure at baseline, 19 showed a rise

above 25 mm with 3 minutes of exercise and 15 of these had their PCWP rise above 18 mm Hg.

Thus a third of patients who have shortness of breath had normal resting hemodynamics with

evidence of diastolic dysfunction with 3 minutes of exercise. These patients had a low VO2 max

on CPET along with a blunted rate of rise of stroke volume curve on Wasserman Curve.

Discussion: We propose that symptomatic patients who undergo right heart catheterization should

be assessed with exercise.

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112

PERICARDIAL DECOMPRESSION SYNDROME: AN ENTITY IN NEED OF URGENT

ATTENTION A. Sinha, A. Singh, R. Kumar, J. Shirani

Saint Lukes University Hospital, Bethlehem, PA, USA

Background: Pericardial decompression syndrome (PDS), defined as paradoxicalhemodynamic

deterioration and/or pulmonary edema, frequently associated with left (LV), right (RV), or bi-

ventricular dilation and systolic dysfunction following pericardiocentesis, has been reported

uncommonly. Pathophysiology of PDS is poorly understood. However, it has been associated with

increased periprocedural mortality.

Methods & Results: We encountered a cluster of 3 cases and a systematic literature search

identified 40 reported cases of PDS [n=43, age 16-91 (mean 48±18) years, 28 (65%) female]. Pre-

procedural echocardiogram showed normal LV ejection fraction in 92% and evidence of

tamponade in 60%. Overall, 23 had percutaneous, 17 had surgical drainage and 3 had both. Volume

of drained pericardial fluid ranged from 450 to 2100 (914±431) ml. Fluid was hemorrhagic in 68%

and underlying etiology was malignancy in 45%. Post-procedurally, ventricular dilation and

systolic dysfunction was noted in LV (57%), RV (43%) or both (29%) ventricles. Peri-procedural

recovery of ventricular function was documented in 96% (27/28), (within days to months) and

mortality was 26% (11/43). Rapid drainage of large pericardial effusion appeared to correlate with

presence and severity of PDS and occurrence of poor outcome.

Conclusions: PDS is being recognized as an important complication of pericardiocentesis with

increasing frequency. Understanding of pathophysiology of this potentially fatal condition requires

a focused approach. Meanwhile, a caution approach to large, chronic pericardial effusion with

stepwise or slow drainage (beyond relief of tamponade) appears warranted for prevention of PDS.

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113

BIOMARKERS IN THE RESPITE TRIAL INVESTIGATING RIOCIGUAT IN PAH

PATIENTS WITH INSUFFICIENT RESPONSE TO PDE-5I J. Klinger1, M.M. Hoeper2, R. Benza3, G. Simonneau4, D Langleben5, R Naeije6,

P.A. Corris7

1. Rhode Island Hospital, Providence, RI, USA

2. Hannover Medical School, Hannover, Germany

3. Allegheny General Hospital, Pittsburgh, PA, USA

4. Bicetre Hospital, Paris-Sud University, Paris, France

5. Jewish General Hospital, Montreal, QC, Canada,

6. Erasme University Hospital, Brussels, Belgium

7. Freeman Hospital, Newcastle-upon-Tyne, UK

Rationale: A significant proportion of pulmonary arterial hypertension (PAH) patients fail to reach

or maintain treatment goals with phosphodiesterase-5 inhibitors (PDE-5i). Because PDE-5i effect

depends on endogenous bioavailability of nitric oxide (NO), NO deficiency may be a key feature

in patients failing PDE-5i treatment. The RESPITE study will investigate whether replacement of

PDE-5i therapy with riociguat, a soluble guanylate-cyclase (sGC) stimulator, can improve clinical

outcome in PAH patients demonstrating insufficient response to PDE-5 inhibition.

Methods: Riociguat directly stimulates sGC independently of NO, potentially restoring the NO-

sGC- cyclic guanosine monophosphate (cGMP) pathway. The RESPITE study is a prospective,

international, multicenter, open-label, single-arm, phase IIIb trial in PAH patients with WHO

Functional Class (FC) III, 6 minute walk distance (6MWD) of 165-440 m, and cardiac index <

3.0 L/min/m2 despite stable doses of sildenafil or tadalafil for at least 90 days. Patients will

undergo a PDE-5i wash-out phase and will then receive therapy with riociguat for 24 weeks. In

addition to clinical endpoints including invasive hemodynamic measurements, echocardiogram,

6MWD, and WHO FC, a number of biomarkers will be explored. These include N-terminal pro-

brain natriuretic peptide, cGMP (from blood and urine), asymmetric dimethyl arginine, growth

differentiation factor 15, and suppression of tumorigenicity 2. These biomarkers will be analyzed

at a central lab prior to initiation of riociguat, at 12 weeks and 24 weeks of treatment.

Conclusion: The characterization of biomarkers relevant to the NO Pathway in PAH patients

enrolled in RESPITE could help elucidate the concept of “NO deficiency” in PAH patients.

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NEW DIAGNOSTIC METHODS AND IMAGING TECHNIQUES / ECHOCARDIOGRAPHY

114 DOBUTAMINE STRESS ECHOCARDIOGRAPHY FOR CARDIOVASCULAR RISK

STRATIFICATION PRIOR TO RENAL TRANSPLANT Y.R. Manda, A. Sinha, S. Agrawal, A. Singh, J. Shirani

St Luke's University Health Network, Bethlehem, PA, USA

Background: Coronary artery disease (CAD) is a major cause of death in renal transplant (RT) candidates with end-

stage renal disease (ESRD). Dobutamine stress echocardiography (DSE) has been used for CAD screening in this

setting, however, data on its prognostic significance is limited.

Methods: Electronic databases (PubMed, ScienceDirect, and COCHRANE) were searched with the MESH terms RT,

DSE, ESRD, and prognosis. Studies were included if they reported on cardiovascular events in patients with ESRD

evaluated for RT.

Results: 7 studies (n=643, 1486 patient years of follow up) met selection criteria (age 52 years, 64% men, 58%

diabetics, 91% hypertensive, 32% smokers and 25% prior CAD). Using pooled data (figure 1a-c), abnormal DSE was

associated with significant increase in MACE [odds ratio (OR)=3.94 (95% confidence interval (CI) 2.27-6.84,

p<0.00001]. Risk of cardiac death (CD) and myocardial infarction (MI) was increased with abnormal compared to

normal DSE [OR=4.77 (95% CI 2.13-10.7), p=0.0001]. Abnormal DSE was associated with higher risk of all-cause

mortality [OR=5.16 (95% CI 1.79 to 14.85), p=0.002].

Conclusions: Patients with abnormal DSE had increased risk of MACE, all-cause mortality and combined CD and MI

during follow up. DSE can be effectively used for risk stratification of patients with ESRD awaiting RT.

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115

UTILITY OF HAND HELD ECHO FOR ASSESSMENT OF LEFT ATRIAL VOLUME

IN CLINICAL SETTINGS V. Ng1, J. Hu1, D. Wong3, P.K. Lee1, P. Nair1, J. Jue1, K. Gin1, M. Barnes1,

D. Thompson2, T.S. Tsang1

1. University of British Columbia, Vancouver, BC, Canada

2. Simon Fraser University, Vancouver, BC, Canada

3. University of Alberta, Edmonton, AB, Canada

Background: Echocardiography (echo) is an essential imaging modality, but in many regions

demand has outpaced the capacity to provide timely results. Current hand-held echo (HHE)

systems have high imaging and computational processing capabilities. While HHE is not

equivalent to a full clinical echo system, it may provide useful point-of-care data in certain

scenarios, enabling treatment decision to be made quickly. We compared the accuracy of HHE

(VScan, GE Medical) versus clinical echo systems for evaluation of left atrial volume (LAV), an

established marker of adverse cardiac outcomes.

Methods: We aimed to assess the concordance between left atrial parameters obtained with a full

clinical echo system and the HHE system. Adults (age >18 yrs) presenting for an outpatient

comprehensive clinical echo were invited to undergo a brief assessment with the HHE system

immediately after the clinical echo. Subjects with congenital heart disorders, prosthetic valves, left

ventricular assist devices or in atrial fibrillation were excluded. We obtained 2D 4-chamber and 2-

chamber views using the HHE, and images were downloaded for offline LAV assessment using

standard biplane area length methods without knowledge of the clinical echo findings.

Results: Clinical echo and HHE images were obtained for 74 subjects (median age 68.5, range 32-

88 years; 39 women). Analysis of calculated LA volume from HHE versus clinical echo showed

a good correlation overall (0.84), without any significant gender effect, but with a marked operator

experience effect; correlations based on the first 20 subjects examined were substantially lower

than for later enrolled subjects (0.81 versus 0.96).

Conclusions: In the hands of a trained and experienced operator, HHE assessment of LAV shows

a high correlation (0.96) with results from a standard clinical echo system. There was a clear cut

learning curve for proficient use of HHE. Point of care utilization of HHE for risk stratification

appeared eminently feasible.

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116

3D ECHO CAN BE USED TO OPTIMIZE PACING ALONG THE LONGITUDINAL

LEFT VENTRICULAR AXIS WHEN USING A MULTIPOLAR LEAD W.B. Cutting, D. Winchester, M. Panna, M. Jansen, J. Petersen, M. Mckillop

University of Florida, Gainesville, FL, USA

During biventricular device placement optimal lead position along the longitudinal axis of the

lateral left ventricular (LV) wall remains a subject of debate. Using the St. Jude Quartet lead, which

features four electrodes and ten pacing vectors, we set out to determine if pacing different sites

along the longitudinal LV axis leads to differences in improved LV dyssynchrony (LVD) as

measured by the systolic dyssynchrony index (SDI). Six veterans underwent implantation of a

biventricular device using the Quartet lead from January to September 2012. Each patient

underwent post-procedure LV volumetric analysis with 3D echocardiography. Mean SDI with

biventricular pacing turned off was compared with LV pacing at different sites along the lateral

LV longitudinal axis. All patients had significant LVD during native conduction, with a mean SDI

of 14.7 +/- 3.2% (5.6% = upper limit of normal). Mean SDI when using the optimal LV pacing

vector for each subject was 4.8 +/- 2.7%, an improvement of nearly 10% (14.7 vs. 4.8, P = 0.006).

When pacing locations along the LV longitudinal axis were compared, only pacing along the mid

LV cavity as opposed to the base and apex provided a statistically significant improvement in

dyssynchrony when compared to native conduction (14.7 vs 5.3, P=0.007).Using 3D

echocardiography following biventricular device implantation with quadripolar LV pacing, we

were able to demonstrate that LVD acutely improves when pacing the lateral left ventricle.

Ventricular dyssynchrony improved the most when pacing the mid lateral LV cavity as opposed

to the base or apex.

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117

DIASTOLIC MYOCARDIAL STIFFNESS ESTIMATED BY ECHOCARDIOGRAPHY

IN PATIENTS WITH AORTIC STENOSIS M.M. Alashry, S.A. Luis, P.A. Pellikka, S.V. Pislaru, C. Pislaru

Division of Cardiovascular Diseases, Mayo Clinic, Rochester MN, USA

Background and Aims: The speed of wave transmission of myocardial stretch has been validated

as a direct measure of myocardial elasticity. We hypothesize this wave speed (Vp) may be

increased in the left ventricular (LV) myocardium of patients with LV pressure-overload (e.g.,

aortic stenosis, AS) due to high LV afterload and its long-term consequences. Our aim was to

determine Vp values in the LV myocardium of patients with severe AS.

Methods: We studied 46 patients with diagnosed severe AS (aortic valve area 0.9±0.2 cm2, mean

pressure gradient 51±14 mmHg, age 72±11 years) and 20 normal controls (age 58±14 years).

Regional Vp (along each LV wall) and global Vp were measured from 3 standard apical views

using customized ultra-high frame rate tissue Doppler. All subjects had comprehensive

echocardiographic exams.

Results: Global Vp was higher in AS compared to controls (1.9±5.8 vs. 1.4±0.2 m/s respectively,

p<0.001). Abnormal Vp (>1.8 m/s, upper value in controls) was found in 52% of patients, despite

normal LV ejection fraction (EF, 65±6%) and nearly normal global longitudinal strain (GLS, -

18.2±2.9%) by speckle tracking. In patients with normal GLS (<-18%), an abnormal Vp was still

found in 10 (22%) patients. Higher Vp was associated with smaller aortic valve areas (p<0.001),

more reduced GLS (p=0.02) and higher filling pressures (E/e’, p=0.002), but not with age

(p=0.107) or EF. A regional heterogeneity in Vp was observed.

Conclusions: Patients with severe AS have increased LV diastolic myocardial stiffness as

estimated by the intrinsic wave method. This increase could be the result of abnormal filling

pressures and tissue properties (e.g., due to fibrosis deposition) that occur with chronically elevated

LV afterload. Noninvasive measurement of myocardial stiffness may be a new imaging biomarker

that may facilitate early identification of structural abnormalities in the LV of patients with severe

AS.

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118

EXERCISE STRESS ECHOCARDIOGRAPHY BETTER PREDICTS MYOCARDIAL

ISCHEMIA THAN EXERCISE ECG IN FEMALE PATIENTS WITH CHEST PAIN S.J. Park1, J.O. Choi1, J.H. Choi1, S.C. Lee1, D.J. Choi2, S.W. Park1

1. Samsung Medical Center, Seoul, South Korea

2. Seoul National University Bundang Hospital, Seongnam, South Korea

Objective: The purposes of this study were 1) to determine the diagnostic accuracy of Exercise

stress echocardiography (ESEcho) in female patients with chest pain, and 2) to evaluate the clinical

outcomes of coronary angiography, revascularization, and cardiac events in Korean female

patients undergoing ESEcho.

Background: ESEcho is sufficiently sensitive and has high enough specificity for the clinical

detection of coronary artery disease (CAD) in women. However, the ability of ESEcho to predict

clinical outcomes in female patients with chest pain remains unknown.

Methods: Over a period of 15 years, 3,396 patients (57±10 yrs) among 3,930 female patients with

chest pain undergoing ESEcho and exercise stress electrocardiography (ESECG) were assessed.

Results: Positive results for ESEcho (newly developed regional wall motion abnormality) were

seen in 134 patients (3.9%). Conventional coronary angiograms or coronary computed tomography

angiograms were obtained for 325 patients (9.6%). Significant coronary artery disease (CAD) was

diagnosed in 30 patients (10 of 260 patients with negative ESEcho results and 20 of 65 patients

with positive ESEcho results). The sensitivity and specificity of ESEcho were 66.7% and 84.8%

respectively. Among 2022 patients with available clinical outcomes, myocardial infarction (MI)

and revascularization occurred more frequently in patients with positive ESEcho results (6.7% vs.

0.1%, p < 0.01). Positive ESEcho was an independent predictor of major adverse cardiac events

(composite of cardiac death, MI, and revascularization) in multivariate analyses.

Conclusions: ESEcho is effective for diagnosing CAD in female Korean patients with chest pain.

Negative ESEcho results were associated with favorable cardiac outcomes, but its prognostic value

needs to be validated in a large-scale prospective study.

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119

CENTRAL OBESITY: AN INDEPENDENT ROLE OR SYNERGISTIC EFFECT TO

METABOLIC SYNDROME ON RIGHT VENTRICULAR STRUCTURE AND

FUNCTION? F.A. Ali, S.W.G. Bakhoum, Z.A. Ashour, D.R. Elremisy

Kasr Al-Ainy Hospital. Cardiology Department, Cairo University, Egypt

Background: The metabolic syndrome (MS) has been shown to affect the right ventricle (RV).

Whether the impact of central obesity (CO) on RV function is independent of the MS is uncertain.

Objective: To assess the impact of CO with or without MS diagnosis on RV structure and function.

Methods: Cross-sectional study of 100 patients (56 women) with CO defined as a waist

circumference (WC) >102 cm in men, >88 cm in women. MS was defined by the presence of ≥ 3

ATP-NCEP-III criteria. All patients were subjected to conventional and tissue Doppler (TD)

echocardiography.

Results: MS was diagnosed in only 57 patients. The RV wall thickness (RVWT), and RV outflow

tract proximal dimension (RVOTPD) were significantly higher (p= 0.008, and p=0.003) in MS

compared to non-MS patients. Tricuspid flow E/A ratio was significantly lower in MS compared

to non-MS patients (p = 0.001). TD derived RV myocardial performance index (MPI) was

significantly higher (p= 0.000) in MS compared to non-MS patients. The tricuspid annular plane

systolic excursion and the RV fractional area change were however similar in MS and non-MS

patients. The independent predictors for RVWT, RVOTPD were WC (ß=0.004, p=0.000 and ß=

0.008, p=0.005 respectively) and systolic blood pressure (SBP) (ß=0.001, p=0.037 and ß=0.004,

p=0.016 respectively), for RV MPI was SBP (ß = 0.003, p= 0.000) and for tricuspid E/A ratio was

age (ß = -0.008, p= 0.000) after multivariable adjustment for WC, age and different components

of MS.

Conclusion: CO in the presence of MS has a greater synergistic impact on RV structure and

function than CO alone. WC and SBP had a significant impact on RV dimensions while SBP alone

had a significant impact on RV function independent of the other components of the MS.

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120

VALUE OF RESTING MYOCARDIAL DEFORMATION ASSESSMENT BY TWO

DIMENSIONAL SPECKLE TRACKING ECHOCARDIOGRAPHY IN DETECTING

THE PRESENCE, AND PREDICTING THE EXTENT AND LOCALIZATION OF

CORONARY ARTERY AFFECTION IN PATIENTS WITH SUSPECTED STABLE

CORONARY ARTERY DISEASE M.A.S. Fahim, S.W.G. Bakhoum, Y.Y. Abdelmoneim, H.S. Taha

Kasr Al-Ainy, Faculty of Medicine, Cairo University, Egypt

Background: Myocardial deformation assessed by 2D speckle tracking echocardiography (STE)

can accurately evaluate regional and global left ventricular (LV) function. Aim: Examine the value

of peak systolic LV strain (S) and strain rate (SR) assessed by STE in detecting, stratifying and

localizing coronary artery disease in stable coronary artery disease (SCAD).

Methods: 81 suspected SCAD patients, normal resting echocardiography, were examined by 2D-

STE and coronary angiography. The global longitudinal strain (GLS)/SR=GLSR; global radial

strain (GRS)/SR=GRSR were calculated as the mean of the sum of S/SR in the 18 segments from

apical views. Mid circumferential strain (MCS)/SR=MCSR were calculated as the mean of S/SR

of the 6 LV segments of the mid cavity short axis view. Significant CAD definition was >50%

diameter stenosis.

Results: Twenty patients had normal coronaries, 27 patients had one/two vessel-CAD (stratified

low risk LR) and 34 patients had three vessel/left main-CAD (stratified high risk HR). GLS,

GLSR, GRS, GRSR, MCS and MCSR were significantly lower in CAD compared to normal

coronaries (p=0.000). By receiver operating characteristic (ROC) curve analysis, GLSR showed

the highest sensitivity (90 %) and specificity (96.7%; AUC=0.98, 95% CI: 0.95-1.0; p=0.000) for

predicting CAD (cut-off value -1.55 1/s). GLS, GLSR, GRSR, MCS and MCSR were significantly

lower in HR compared LR (p=0.03, p=0.009, p=0.000, p=0.000, and p=0.004 respectively); whilst

MCS best differentiated LR from HR (cutoff value -20.87%, sensitivity: 88.9 %, specificity:

76.5%, AUC=0.83, 95% CI: 0.73-0.94; p=0.000). ROC curve analysis showed the mean of

longitudinal strains of the anterior wall and septum to best predict LAD disease (sensitivity=90%,

specificity=91.1%). Mean longitudinal strain of posterior and lateral wall segments best predicted

LCX disease (sensitivity=95%, specificity=80%). Mean circumferential strain of mid inferior wall

best predicted right coronary disease (sensitivity=83.3%, specificity=78.8%).

Conclusion: STE calculated myocardial deformation diagnoses, stratifies and localizes CAD in

SCAD.

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121

IMPROVEMENTS IN LEFT ATRIAL APPENDAGE VELOCITIES FOLLOWING

TRANSCATHETER AORTIC VALVE REPLACEMENT T. Ando1, D. Slovut2, C. Taub2

1. Mount Sinai Beth Israel

2. Montefiore Medical Center, New York, NY, USA

Objectives: We aimed to assess the effect of transcatheter aortic valve replacement (TAVR) on LAA

emptying and filling velocities.

Background: Left atrial appendage (LAA) is a common source of systemic thromboembolism. LAA

velocity predicts future thromboembolism risk.

Methods: Medical records of patients who underwent TAVR at a single center were retrospectively

reviewed. LAA velocities were recorded before and after TAVR by transesophageal echocardiography.

Low flow-low gradient severe aortic stenosis (LFLG-SAS) patients were defined as stroke volume

index < 35 ml/m2 and mean aortic pressure < 40 mmHg. Patients with persistent atrial fibrillation were

excluded.

Results: Forty-five patients were included. Mean age was 79±9, male was 51%. There were 12 (27%)

LFLG-SAS patients. LAA emptying and filling velocity pre and post TAVR for LFLG-SAS patients

were 30.8 (21.6-50.9) cm/sec vs 42.4 (38.8-55.4) (p<0.01) cm/sec and 31.5 (22.2-36.5) cm/s vs 39.6

(31.8-53.4) (p<0.01) cm/s, respectively (Figure 1) whereas for non-LFLG-SAS patients it was 29.5

(19.7-37.3) cm/s vs 30.3 (21.0-42.7) (p=0.42) and 29.5 (19.7-37.3) vs 25.7 (21.2-39.7) (p=0.86),

respectively.

Conclusions: Our study showed improved LAA velocities in LFLG-SAS patients shortly after TAVR

but not in non-LFLG-SAS patients. Whether these improvements translates into future fewer

thromboembolic events needs further study.

Figure 1

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VASCULAR DISEASE (PERIPHERAL AND CAROTID), AORTIC DISEASES

122

INVESTIGATION OF GRAVITY OF THORACIC AORTIC ATHEROSCLEROSIS

COMPARED TO AGE, SEX AND PRESENCE OF THROMBOUS IN LEFT ATRIAL

APPENDAGE G.D. Spyromitros, I.K. Lagos

Katerini General Hospital, Greece

Aim: The purpose of this study is to investigate the existence or non-correlation between the

severity of atherosclerosis of the thoracic aorta with age, gender and the presence of thrombus in

the left atrial appendage

Methods: 39 adults (15 women, 24 men) who underwent transesophageal ultrasound this year in

our clinic were used to collect the data. The parameters studied were the thickness of the plaque at

the level of thoracic aorta mm xo, 1, the presence of contrast media, the presence of thrombus in

the left atrial appendage and the flow rate of the flap of the left atrium.

Results: From the analysis of the data showed correlation between the severity of the

atherosclerotic thoracic aorta with increasing age (r=0.567, p<0.01). It was also shown that the

incidence of atherosclerosis of the thoracic aorta is greater in men (r=0.595, p<0.01) than women

(r=0.530, p=0.02). Further analysis of the data revealed the presence of echo contrast at 33.3% of

the total examined, the presence of thrombus in the left atrial appendage at a rate of 33.3% and in

the presence of low flow velocity in patients they brought thrombus in left atrial appendage. The

percentage of women with thrombus in the left atrial appendage was 46% (7 out of 15) and the

percentage of men with thrombus in the left atrial appendage was 25% (6 out of 24).

Conclusions: There is positive correlation between the severity of atherosclerosis of the thoracic

aorta with increasing age with greater incidence observed among men compared with women.

Presence of thrombus in the left atrial appendage appeared more frequent in women rather than

men in patients with atherosclerotic thoracic aorta.

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VASCULAR DISEASE (PERIPHERAL AND CAROTID), AORTIC DISEASES

123

PROFILES AND PROGNOSIS OF PATIENTS WITH SEVERE CAROTID

ARTERIOSCLEROSIS T. Tomaru1, N. Seneviratne2, T. Ariyama3, T. Matsubara4, E. Matsubara4, T. Nakajima4,

T. Tsutsumi1

1. Toho University Sakura Hospital, Sakura, Japan

2. Anuradhaputa Teaching Hospital

3. Toho University Department of Pharmacology

4. Tokyo University Hospital, Japan

There have been few reports on prognosis of severe carotid sclerosis in association with other

cardiovascular disease.

Methods: Severe carotid sclerosis was diagnosed by carotid ultrasonography, and plaque score

(PS) was calculated by summation of max thickness of each plaque. 242 patients with severe

carotid sclerosis•iSCS: PS more than 10•jwere studied and compared those with mild carotid

sclerosis•iMCS: PS less than 5•j. Patients with significant carotid stenosis (more than 50% in

diameter) were excluded. The 262 patients with MCS were compared.

Results: In patients with SCS, mean age was 72.7, and mean PS was13.8. Cerebral infraction (CI)

was observed in 76 patients(31.4%). Cardiovascular disease was observed in 95(39.2%), and

coronary artery disease (CAD) only was observed in 71 (29.3%). Antiplatelet therapy had been

done in 46% of patients with SCS and in 12% of MCS. In patients with MCS, mean age was 69.5,

and mean PS was 3.82. CI was observed in 28 patients(10.69%)•iP=0.0001 vs

SCS•jCardiovascular disease was observed in 26 patients(9.92%),and coronary artery

disease(CAD) only was observed in 20(7.63%)(P=0001 vs SCS). In 3 year follow up, CI developed

in 8 out of 242 with SCS, and in 4 out of 262 patients with MCS. All patients who developed CI

had other cardiovascular disease. Mean number of risk factor was 2.2•1.1 in patients who

developed CI and 1.8•

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BIOCHEMICAL MARKERS FOR RISK ASSESSMENT IN CARDIOVASCULAR DISEASES

124

SERUM CYSTATIN C IN PATIENTS WITH CORONARY STENTS AND RISK OF

RESTENOSIS N.V. Goncharova1, G.S. Russkikh2, Ts.P Korolenko1, K.V. Loktev1, T.A. Korolenko1

1. Institute of Physiology and Fundamental Medicine SB RAMS, Novosibirsk, Russia

2. Institute of Biochemistry SB RAMS, Novosibirsk, Russia

Objectives: To investigate whether patients with atherosclerosis after coronary stenting display

altered serum cystatin C as a possible biomarker of acute ischemia.

Background: The incidence of coronary restenosis after stent placement is high, especially in the

1-year follow-up. Inflammation plays an important role in the pathogenesis of in-stent restenosis,

causing neointimal proliferation through the stent meshes. Subsequent in-stent restenosis may

affect the long-term safety and efficacy of angioplasty and stenting. Cystatin C was recently

suggested as a candidate biomarker in cardiovascular pathology.

Methods: 34 male patients (61.8 ± 7.3 years) treated by anticoagulant therapy were enrolled in a

study from the Outpatient Clinic N 1 of Novosibirsk (6 mos - 1 year after coronary stenting). The

control group consisted of 25 healthy persons (50-65 years old). Serum CRP-hs, D-dimer

(Architect C-8000, USA) and Cystatin C by ELISA kit for humans (BioVendor, Czechia) were

measured in all groups. Results. In healthy persons, aged 50-65, an elevation of serum cystatin C

(1.11± 0.23 mg/L, p< 0.01) was shown vs. healthy persons, aged 20-40 years. In patients with

coronary stents, there was a significant increase in serum CRP-hs (p < 0.001), D-dimer (p < 0.001)

and cystatin C (2.05 ± 0.21 mg/L, p < 0.001) vs the control (aged 50-65). Positive correlation was

shown between cystatin C and d-Dimer in stenting patients (r = 0.45; p < 0.05).

Conclusions: Serum cystatin C is elevated in patients with coronary stenting, as well as CRP-hs,

indicating on inflammation, increased risk of in-stent restenosis and ischemia.

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125

IS THERE ANY CORRELATION BETWEEN PLATELET INDICES WITH EXTENT

OF CORONARY ARTERY INVOLVEMENT AMONG PATIENTS WITH ISCHEMIC

HEART DISEASES? S.M.H. Adel, B. Pyami, S.M. Seyedian, M. Saghatoleslami, M. Jafarsalehi, S.H. Zakerin,

S. Bagheri, M. Noorizadeh

Atherosclerosis Research Center, Ahwaz Jundishapur University of Medical Sciences,

Ahwaz, KH, Iran

Objective: Ischemic heart diseases (IHD) is the most common form of heart disease and death

across the world. Nowadays Platelet counts (PC) and volumetric platelet indices using automatic

counters are available routinely in most laboratories and reflect the level of mobility and the

production of platelets. It seems that the excessive flexibility of the platelets and their local

activation have a major role in acute coronary events. So, our objective is the study of platelet

indices in ischemic heart disease and trying to find out a clinical-pathological correlation.

Materials and methods: This non-randomized prospective study was performed on 247 patients

with ischemic heart disease, who underwent the coronary angiography. The patients were divided

into four groups: stable angina, unstable angina, acute myocardial infarction and control group;

and then platelet indices, including the platelet counts (PC), the average platelet volume (MPV),

the Platelet Distribution Width and plateletcrit (PCT) in each group with the extent of coronary

disease were compared based on an Syntax Score System.

Results: The average ages of the patients were 57 years and 65% of them were male and the rest

were female. A significant difference existed between indexes in all three groups compared to the

control that this difference was related to gender and the type of the disease however, only in

infarction group, PDW in different disease intensities was significantly different.

Conclusion: In this study, unlike many of the previous studies no relationship was found between

the MPV with the extent of coronary disease.

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126

THE DIAGNOSTIC VALUE OF THE NEUTROPHIL-LYMPHOCYTE RATIO IN

STROKE RECOGNITION M. Rukshin1, N. Jessani2, M. Medina2, V. Rukshin2

1. Holmdel High School, Holmdel, NJ, USA

2. Raritan Bay Medical Center, Old Bridge, NJ, USA

Background: The role of the neutrophil-lymphocyte ratio (NLR) in stroke diagnosis has not been

thoroughly evaluated. The NLR has been recognized as a marker of inflammation. Since a stroke

causes local inflammation, the NLR should be influenced. However, since this inflammation is the

result of aseptic damage of the relatively small affected area of the brain, an NLR that is

excessively divergent from the average value decreases the likelihood of a stroke's presence. The

NLR can be calculated using a routine blood test.

Objective: This study determined the diagnostic value of the NLR in stroke recognition.

Methods: Data of all incoming patients with suspected stroke from Raritan Bay Medical Center

over the period of 3 years (2010-2013) was collected. The significance of age, sex, smoking,

presence of diabetes, abnormal renal function, and dyslipidemia was ruled out using the t-test and

chi-squared test. The Receiver Operating Characteristic (ROC) for different NLR values was

compared by constructing ROC space, ROC inverse charts, and ROC contingency tables.

Results: The study revealed the inverse correlation between the NLR and stroke presence. An NLR

above 4.0 decreases the likelihood of the presence of a stroke, while an NLR lower than 4.0 makes

the diagnosis of a stroke more probable in patients with stroke-like symptoms.

Conclusion: The NLR has diagnostic value in stroke recognition. It can be used as a tool in ruling

out the presence of a stroke.

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PREVENTION OF CARDIOVASCULAR DISEASE: ASSESSMENT AND MANAGEMENT OF CARDIOVASCULAR RISK

127

CLINICAL IMPACT AND COST-EFFECTIVENESS OF TREADMILL TEST IN

ASYMPTOMATIC INDIVIDUALS E.H. Park1, G.M. Park1, T.S. Kim1, C.J. Kim1, J.S. Cho1, M.W. Park1, S.H. Her1,

J.B. Kwon2, Y.R. Cho3

1. Department of Cardiology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic

University of Korea, Daejeon, Korea

2. Department of Cardiothoracic surgery, Daejeon St. Mary's Hospital, College of Medicine, The

Catholic University of Korea, Daejeon, Korea

3. Department of Cardiology, Dong-A University Hospital, Busan, Korea

Objectives: The purpose of this study was to investigate the clinical impact and cost-effectiveness

of treadmill test in asymptomatic individuals.

Methods and Results: We analyzed 8,694 propensity-score matched asymptomatic individuals

aged 18 years and older with no prior history of cardiovascular disease who underwent self-referral

treadmill test evaluation as part of a general health examination (treadmill test [n=2,898] versus

control [n=5,796]). Clinical outcome was defined as a composite of all-cause death, myocardial

infarction, and stroke in 1 year after the index test. Subsequent use of cardiac tests, total medical

costs, and coronary artery disease (CAD)-related medical costs were investigated within 6 months

of the index test. Compared with the matched control group, the treadmill test group underwent

further cardiac tests (3.90% versus 2.43%, p<0.001). However, coronary revascularizations were

less frequently performed in the treadmill test group (0.03% versus 0.21%, p<0.001) and the

primary composite clinical outcome was not statistically different between the two groups (0.14%

versus 0.28%, p=0.157). Total medical costs were higher in the treadmill test group ($544 versus

$492, p=0.045), but CAD-related costs were not different between the two groups ($12 versus $15,

p=0.611) for 6 months. However, considering the baseline cost of a treadmill test ($42), the

treadmill test group had higher 6-month CAD-related medical costs (p<0.001)

Conclusions: In asymptomatic individuals, screening with treadmill test was associated with

higher subsequent cardiac tests and medical costs, but did not decrease the 1-year risk of death,

myocardial infarction, and stroke.

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128

MODEL FOR ASSESSING CARDIOVASCULAR RISK IN A KOREAN POPULATION E.H. Park1, G.M. Park1, D.W. Kim1, T.S. Kim1, C.J. Kim1, M.W. Park1, S.H. Her1,

J.B. Kwon2, Y.R. Cho3, Y.H. Kim4

1. Department of Cardiology, Daejeon St. Mary's Hospital, the Catholic University of Korea,

Daejeon, Korea

2. Department of Cardiothoracic Surgery, Daejeon St. Mary's Hospital, College of Medicine, The



4. Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine,

Seoul, Korea

Background: A model for predicting cardiovascular disease in Asian populations is limited.

Methods and Results: In total, 57,393 consecutive asymptomatic Korean individuals aged 30 to 80

years without a prior history of cardiovascular disease who underwent a general health

examination were enrolled. Subjects were randomly divided into the train (n=45,914) and

validation (n=11,479) cohorts. Thirty-one possible risk factors were assessed. The cardiovascular

event was a composite of cardiovascular death, myocardial infarction, and stroke. In the train

cohort, the C-index (95% confidence interval) and Akaike Information Criterion were used to

develop the best-fitting prediction model. In the validation cohort, the predicted versus the

observed cardiovascular event rates were compared by the C-index and Nam and D'Agostino X2

statistics. Over a median follow-up period of 3.1 (interquartile range, 1.9–4.3) years, 458 subjects

had 474 cardiovascular events. In the train cohort, the best-fitting model consisted of age, diabetes

mellitus, hypertension, current smoking, family history of coronary heart disease, white blood cell,

creatinine, glycated hemoglobin, atrial fibrillation, blood pressure, and cholesterol (C-index=0.757

[0.726–0.788] and Akaike Information Criterion=7,207). When this model was tested in the

validation cohort, it performed well in terms of discrimination and calibration abilities (C-

index=0.760 [0.693–0.828] and Nam and D'Agostino X2 statistic=0.001 for 3 years; C-

index=0.782 [0.719–0.846] and Nam and D'Agostino X2 statistic=1.037 for 5 years).

Conclusion: A risk model based on traditional clinical and biomarkers has a feasible model

performance in predicting cardiovascular events in an asymptomatic Korean population.

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129

CARDIOVASCULAR RISK AND HEALTH-RELATED QUALITY OF LIFE (HRQOL)

AMONG HIV-POSITIVE PATIENTS IN US HOUSEHOLD POPULATION: THE

NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY (NHANES)

1999-2012 J.H. Sung1, J.Y. Lee2, J.E. Lee1

1. Jackson State University, Jackson MS, USA

2. University of Miami, Miami, FL, USA

Cardiovascular disease has emerged as a problem among HIV-infected population and may have

a profound impact on quality of life. Although previous studies found a higher cardiovascular risk

linked to worse health-related quality of life (HrQoL) among general population, limited studies

have been conducted for HIV patients. This study is to characterize HIV-positive adults in

household population in terms of cardiovascular risk and HrQoL using large national survey

datasets.

Methods: The analyses utilized the data of NHANES 1999-2012 which included a valid sample of

119 HIV-positive cases and 357 HIV-negative controls matched by age, gender, race, and survey

year. Cardiovascular risk was measured by using Framingham 10-year risk scores. HrQoL was

measured by using the CDC 4-item HrQoL. A series of conditional logistic regression analyses

was conducted to determine the difference of cardiovascular risk and HrQoL between HIV-

positive and –negative adults.

Results: Among 119 HIV-positive patients, 72.4% were male and 66.4% were African Americans.

Their mean age was 39.1(±8.6). A lower level of HDL (p<0.0001), Framingham 10-year

cardiovascular risk (p=0.0659), waist circumference (p=0.0074), and BMI (p=0.0016) was

observed among cases. Controls reported a lower level of number of days mental health was not

good (p=0.0581), inactive days due to mental and physical health (p=0.0002), LDL (p=0.0314),

and times received healthcare in past year (<0.0001). Cases were more likely to have at least one

disease history (p=0.0338) and a higher prevalence of chronic kidney disease (6.3% for cases and

1.3% for controls; p=0.0275).

Conclusion: Our study found that although HIV-positive cases had favorable anthropometric

measurement and cardiovascular risk, they had worse health-related quality of life and received

healthcare more frequently. However, it was not clear that worse HrQoL was caused by

cardiovascular risk heightened by HIV infection. Further study is needed to examine the cause of

worse health status of HIV-positive patients, controlling for anti-retroviral therapy and stage of

HIV.

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130

THE DEVELOPMENT OF A LIFESTYLE INTERVENTION PROGRAM FOR PEOPLE

WITH METABOLIC SYNDROME: BASED ON THE HEALTH BELIEF MODEL S.W.S. Lo, S.Y. Chair, F.K. Lee

The Nethersole School of Nursing, The Chinese University of Hong Kong, HKSAR

Background: Lifestyle intervention is advocated for people with metabolic syndrome (MS).

However, interventions delivered across reviewed studies were inconsistent and insufficient to

meet the needs of a Chinese population. Moreover, the lack of conceptual guidance limited the

study’s ability to explain the corresponding outcomes. In regard to the high prevalence of MS, an

effective lifestyle intervention program by scientific approach is important for people with MS.

This study aimed to develop a lifestyle intervention program by identifying needs from the targeted

population as guided by the extended Health Belief Model (eHBM).

Methods: A cross-sectional survey based on eHBM was conducted to assess health behaviors and

health beliefs on 132 Chinese with two or more MS components. Hierarchical regression approach

was used to analyze the survey data. Synthesizing the survey results with current

recommendations, a lifestyle intervention program (LIPMS) was developed.

Results: Self-efficacy and perceived barriers were found to have high predictive values to health

behavior. These results provided directions for the development of LIPMS. LIPMS is a twelve-

week program containing three components: two weekly group educational sessions, one brief

individual counselling, and two telephone calls. The effects of LIPMS was tested in another RCT

study and regarded as effective in terms of improving health outcomes and health behavior.

Conclusions: The use of the eHBM provides a conceptual framework to guide the development of

LIPMS for people with MS. Lifestyle intervention program should include practical strategies to

increase participant’s self-efficacy for overcoming barriers perceived.

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HYPERTENSION: BASIC, CLINICAL AND EPIDEMIOLOGICAL

131

INFLUENCE OF ALBUMINURIA ON AMBULATORY BLOOD PRESSURE

REGULATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE: THE HYGIA

PROYECT D.E. Ayala1, A. Otero2, J.J. Crespo3, M. Dominguez-Sardina3, P.A. Callejas3, L. Pousa3,

E. Sineiro4, S.M. Gomara4, A. Moya4, R.C. Hermida1

1. University of Vigo, Vigo, Spain

2. Complejo Hospitalario Universitario, Ourense, Spain

3. Servicio Gallego de Salud, Vigo, Spain

4. Servicio Gallego de Salud, Pontevedra, Spain

Objectives: Sleep-time hypertension and the non-dipper blood pressure (BP) profile determined

by ambulatory BP monitoring (ABPM) are highly prevalent in chronic kidney disease (CKD).

Although presence of kidney damage is intrinsic to the current definition of CKD, stratification of

patients according to disease stages has been frequently based on estimated glomerular filtration

rate (eGFR) alone, independent of presence or absence of albuminuria. We evaluated the potential

influence of albuminuria on ambulatory BP in patients with stage 3-5 CKD participants in the

Hygia Project, designed to evaluate prospectively cardiovascular, metabolic, and renal disease risk

by ABPM in primary care centers of Northwest Spain.

Methods: This study involved 3339 patients with stage 3-5 CKD (eGFR <60 ml/min/1.73 m2 at

least twice within 3 months), 1816 men/1523 women, 69.1±11.9 years of age. Among them, 1073

had albuminuria (albumin/creatinine ratio >30 mg/gCr). BP was measured at 20-min intervals from

07:00 to 23:00h and at 30-min intervals at night for 48h.

Results: Ambulatory BP was significantly higher in patients with than without albuminuria, mainly

during the nighttime sleep span (awake/asleep BP means of systolic BP 137.0/129.0 vs.

131.1/122.2 mmHg, respectively, P<0.001). The sleep-time relative BP decline was significantly

attenuated (5.6 vs. 6.7%, P<0.001) and, accordingly, the prevalence of the non-dipper/riser BP

pattern significantly greater (67.8 vs. 63.2, P=0.002) in patients with albuminuria. Prevalence of

sleep-time hypertension (asleep BP >120/70 mmHg) was also significantly larger in patients with

albuminuria (70.3 vs. 56.2, P<0.001).

Conclusions: Our findings document the extremely high prevalence of altered circadian BP

patterning in patients with CKD. Prevalence of sleep-time hypertension and/or non-dipper BP

patterning, documented relevant prognostic markers of increased cardiovascular risk, was

significantly greater in the presence of albuminuria. These findings corroborate the need to use

both eGFR and albuminuria for proper stratification of patients according to CKD stage severity.

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132

THE RISK FACTORS THAT PREDICTING THE OCCURRENCE OR PROGRESSION

OF CHRONIC HYPERTENSION IN POSTPARTUM PERIOD IN WOMEN WITH A

HISTORY OF PREECLAMPSIA J.W. Hwang1, S.J. Park1, S.Y. Oh1, C.H. Choi1, S.C. Lee1, D.J. Choi2, S.W. Park1



Purpose: Preeclampsia (PE) was one of the most important pregnancy complications to bring

about the lethal effects to mothers, in addition this is associated with the subsequent development

of future chronic hypertension. The purpose of this study was to identify the clinical risk factors

progressing to the chronic hypertension in postpartum period in the women diagnosed with PE.

Methods: We included the 659 patients who were delivered as diagnosed with PE in index

pregnancy. According to the subsequent development of chronic hypertension, we divided two

groups as case group (n=73), presenting the chronic hypertension and normal control group

(n=586). The clinical and demographic factors were evaluated. The duration of median follow-up

was 51.2±31.8 months.

Results: By multiple regression analysis, high blood pressure in first trimester, comorbidities as

renal disease, systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APLS),

vascular disease, and higher body mass index (BMI) at previous pregnancy were associated with

the progression of chronic hypertension in postpartum period. The incremental pattern of area

under receiver operating characteristics (AUROC) for seven models, from 0.619 to 0.818, showed

that the prediction of progression on the chronic hypertension improved to add the significant risk

factors by multivariate analysis stepwise.

Conclusions: This retrospective registry demonstrated that the clinical risk factors as high blood

pressure in first trimester, higher BMI, and comorbidities (renal disease, SLE or APLS, and

vascular disease) were significantly independent predictors, which can identify the women at a

risk of developing future chronic hypertension after delivery. Through identifying these risk

factors for evaluating the capacity of progression, we could decide the particular women for

monitoring and managing the high blood pressure in postpartum period.

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133

DIAGNOSTIC ACCURACY OF OFFICE BLOOD PRESSURE MEASUREMENT

ACCORDING TO SEX AND AGE S.H. Kim1, J.J. Park1, H.Y. Lee2, S.H. Park3, J.H. Shin4, D.J. Choi1

1. Seoul National University Bundang Hospital, South Korea

2. Seoul National University Hospital

3. Severance Hospital

4. Hanyang University Guri Hospital

Objectives: To evaluated the diagnostic accuracy of office blood pressure (OBP) measurement.

Background: The OBP measurement is subject to many biases. Women have higher office BP, and

older patients higher pulse pressure, so that the diagnostic accuracy of OBP may be lower in those

patients.

Methods: We evaluated the diagnostic accuracy of OBP compared with 24-hour ambulatory BP

(ABP) as reference BP in 1.028 patients. Hypertension was defined as systolic BP>140mmHg,

and/or diastolic BP>90mmHg.

Results: The mean age was 58 years, 49% were male. The mean office systolic and diastolic BP

was ±17mmHg and 84±12mmHg, respectively, and they were higher than those of ABP (SBP,

123±13mmHg; DBP, 78±11mmHg) (paired T-test P<0.001). There was only a week correlation

between the OBP and ABP (r=0.180, P<0.001). Overall 44% showed discordance; 23% had false

positive and 21% had false negative results. Women had twice higher false positive results than

men (29% vs. 15.7%, p < 0.001), while men had higher false-negative results (25.9% vs. 17.3, P

< 0.001). As for the age, the concordance rate was highest among patients <20 years (87.5%) and

>80 years (78.8%), whereas in middle aged group it was around 55%.

Conclusions: The diagnostic accuracy of OBP is low. Women have higher false-positive, men

higher false-negative results. High discordance between OBP and ABP indicates suboptimal

management of hypertensive patients in both men and women. The use of ABP should be

considered in all hypertensive patients.

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134

ABNORMAL CAROTID ARTERIAL MECHANICS DESPITE NORMAL INTIMA-

MEDIA THICKNESS IN PATIENTS WITH DIABETES MELLITUS OR

HYPERTENSION S.A. Kim1, S.H. Jo1, K.H. Park1, H.S. Kim1, S.J. Han1, W.J. Park1, J.W. Ha2

1. Hallym Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea

2. Severance Cardiovascular Hospital, Yonsei University College of Medicine, South Korea

Background: Carotid intima-media thickness (cIMT) is an established surrogate marker of

atherosclerosis. However, cIMT may not reflect the whole arterial changes occurring in various

pathologic conditions, such as diabetes or hypertension.

Objective: The aim of this study was to evaluate whether vascular properties of CA differed in

patients with hypertension or diabetes who have normal cIMT.

Methods: Vascular properties of CA were assessed in 402 consecutive asymptomatic subjects who

have normal cIMT (151 patients with diabetes mellitus, 131 with hypertension, and 120 age- and

gender-matched controls). Conventional carotid stiffness indices, including beta stiffness,

distensibility coefficients and elastic modulus calculated from vessel diameter and blood pressure,

and parameters from velocity-vector imaging (VVI), including vessel area, fractional area change

(FAC), radial velocity, circumferential strain, and strain rate of CA were measured to assess the

differences between the groups.

Results: Both patients with hypertension and diabetes showed higher elastic modulus, lower

distensibility coefficients and FAC by VVI when compared to those of controls. However, when

adjusting for baseline covariates, there was no more differences of mechanical properties of CA

between patients with diabetes and controls. Only patients with hypertension showed lower FAC

than controls and larger vessel area than both controls and diabetes, independent of baseline

covariates.

Conclusion: Despite normal cIMT, the CA of hypertensive patients was stiffer and positive

remodeling preceded the wall thickening independent of baseline covariates, whereas vascular

properties of patients with diabetes were not different from that of controls after adjustments.

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135

EFFECT OF TREATMENT OF HYPERURICEMIA WITH FEBUXOSTAT IN

HYPERTENSIVE PATIENTS WITH CHRONIC HEART FAILURE AND CHRONIC

KIDNEY DISEASE T. Naka1, A. Sumiyoshi2, T. Ando2, M. Shibuya2, T. Masuyama2

1. Department of Internal Medicine, Kaizuka City Hospital, Kaizuka, Japan

2. Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Japan

Background: Febuxostat, a non-purine xanthine oxidase inhibitor, has been reported to have a

stronger effect and more safety on hyperuricemia than allopurinol. However, there is not available

on the effect of febuxostat in hypertensive patients with chronic heart failure (CHF) and chronic

kidney disease (CKD).

Methods: The aim of this study is to examine the efficacy and safety of febuxostat in hypertensive

patients with CHF and CKD for treating hyperuricemia. Twenty hyperuricemic patients with

hypertension (HT), CHF and CKD were enrolled and treated with febuxostat (10-20mg/day).

Serum uric acid concentrations and serum estimated GFR levels in the 3 months before and after

the start of febuxostat treatment were collected for HT, CHF and CKD patients switched from

allopurinol after failing to achieve serum uric acid concentrations <6.0mg/dL.

Results: Evaluable data were available for 20 patients, 20% of whom had advanced CKD

(eGFR<30mL/min/1.73m2). Mean dose of febuxostat was 11 (±3.7) mg/day. By using febuxostat,

mean serum uric acid concentration decreased from 7.6 (±1.2) mg/dL at baseline to 6.2 (±0.9)

mg/dL at 3 months (p<0.001); 35% of patients achieved a level <6.0mg/dL. No serious adverse

reactions were noted with febuxostat, and there were no significant changes in blood pressure,

heart rate, total cholesterol, triglyceride, hemoglobin A1c, and hepatic and renal function.

Conclusions: Febuxostat was effective for hyperuricemia in patients with HT, CHF and CKD

without severe side effects.

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MECHANISMS OF ACUTE CORONARY SYNDROME: FROM BENCH TO BEDSIDE

136

EARLY DETECTION OF UNSTABLE CARDIAC LESIONS IN ASYMPTOMATIC

INDIVIDUALS AT RISK OF ACUTE CORONARY SYNDROME A. Simonini, D.S. Harrington

1. Cedars Sinai, Heart Institute, Los Angeles, CA, USA

2. University of Southern California, Keck School of Medicine, Los Angeles, CA, USA

Coronary artery disease (CAD) remains the world’s leading cause of death (7 million annually).

Initial CAD presentation for most patients is acute coronary syndrome (ACS) from rupture of non-

obstructive unstable plaque. Screening for ACS risk remains a challenge; traditional risk factors,

multi-factorial absolute risk methods, and standard noninvasive testing predict only 60-65% of

cardiovascular risk. Plaque rupture results from an inflammatory injury/repair process underlying

the formation, progression, and eventual rupture of unstable thin-cap atheromas. Although active

inflammation is increased in ACS patient plaques, smoldering inflammation characterizes unstable

silent plaque. We undertook clinical trials to identify predictive biomarkers constant in atheroma

progression to unstable lesions as a result of inflammatory pathway activation, and developed a 9-

protein/4 clinical risk factor algorithm for identification of at-risk patients frequently missed by

current methods (CTACK, Eotaxin, Fas Ligand, HGF, IL-16, MCP-3, sFas, Hba1c, HDL; age,

sex, diabetic status, and family history). Longitudinal outcome-based cohorts, disease free at

baseline, represented 31,569 individuals; Cases/Controls totaled 1,634/4,474. Measuring baseline

serum samples from 1,084 CAD-free individuals, 362 of which subsequently developed CAD,

optimized biomarker assay panels. Using an optimum size model predicted by the drop-in-

deviance approach, a multivariate Cox proportional hazard regression model was fit using the most

powerful predictors within the clinical and protein variables. A multi-ethnic case-cohort sample

(MESA) was used for external validation. The Biomarker Algorithm detected 46% of ACS patients

missed by current methods in the Intermediate Risk group (clinical Net Reclassification Index 43%

from initial FRS), and, when combined with lipids, correctly identified 61% of ACS patients. We

conclude that the algorithm demonstrates clinical utility in identifying patients with unstable

cardiac lesions frequently missed by current evaluations, and predicts how likely these apparently

healthy individuals are to experience an ACS, enabling preventative therapies to be initiated in

individuals who might benefit most.

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137

INTRACRANIAL HEMORRHAGE FOLLOWING FIBRINOLYSIS FOR ACUTE ST

SEGMENT ELEVATION MYOCARDIAL INFARCTION S. Agrawal, Y. Manda, R. Durkin, P. Puleo, J. Shirani


Background: Intracranial hemorrhage (ICH) is a recognized complication of fibrinolysis for ST

elevation myocardial infarction (STEMI). Data on predictors and outcome of ICH in this setting

is limited.

Methods: Adult STEMI patients treated with fibrinolysis were identified from the National

Inpatient Sample (NIS) database from 2003-2011 using ICD9 codes. A retrospective analysis of

baseline demographics, clinical characteristics, comorbidities and outcomes was performed.

Results: ICH was reported in 738 (0.9%) of 85,187 acute STEMI patients treated with fibrinolysis.

ICH was associated with significantly higher in-hospital mortality [54.7% vs. 4.5%, adjusted odds

ratio (OR) = 20.54, p<0.001]. When compared to those without ICH, patients with ICH were older

(71-vs-61.3 years, p <0.001) and were more often women (50.8%-vs-29.9%, p<0.001) No

significant racial differences were identified. ICH patients were more likely to have pre-existing

coagulopathy (3.8%-vs-2.2%; p=0.003), renal failure (11-vs-4.8%; p<0.001) and hypertension

(65.9%-vs-55.3%; p<0.001). Stepwise logistic regression analysis identified older age (≥65yrs)

(OR 2.51, p <0.001); female sex (OR 1.72, p<0.001);); hypertension (OR 1.31, p=0.04) and

alcohol abuse (OR 2.3, p<0.001) as independent predictors of ICH. White race (OR 0.80, p=0.044)

and obesity (OR 0.21, p<0.001) were independent negative predictors. Diabetes mellitus, renal

failure, coagulopathy and treatment at either rural or non-teaching hospitals were not found to be

independent predictors of ICH.

Conclusions: ICH following fibrinolysis for STEMI is relatively uncommon. It occurs more

commonly in older women and those with hypertension and alcohol abuse, and is associated with

greatly increased in-hospital mortality.

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138

PROGNOSTIC VALUE OF ST-SEGMENT MORPHOLOGY IN FIRST ANTERIOR ST-

SEGMENT MYOCARDIAL INFARCTION N. Misumida1, A. Kobayashi1, Y. Kanei2

1. Department of Internal Medicine, Mount Sinai Beth Israel, New York, NY, USA

2. Department of Cardiology, Mount Sinai Beth Israel, New York, NY, USA

Background: The morphology of ST-segment elevation has been mainly investigated regarding its

diagnostic value for acute myocardial infarction. We aimed to clarify the prognostic value of the

morphology of ST-segment in patients with ST-segment elevation myocardial infarction (STEMI).

Methods: We carried out a retrospective analysis of 167 consecutive first anterior STEMI patients

who underwent coronary angiography. Patients with prior myocardial infarction, bundle branch

block or ventricular paced rhythm were excluded. ST-segment morphology was classified into

concave or non-concave (straight or convex) patterns based on the shape of the ST-segment in the

lead with maximal ST-segment elevation. Baseline characteristics, echocardiographic and

angiographic findings, as well as in-hospital and 1-year all-cause mortalities were compared

between the two groups.

Results: Of the 167 patients, 84 patients (50%) had concave pattern. Patients with concave pattern

had a lower prevalence of diabetes than those with non-concave pattern. Patients with concave

pattern had a significantly lower rate of Killip class 3 or 4 on presentation (6% vs. 16%, p=0.04).

There was no statistically significant difference between the two groups in peak creatine kinase

value (median; 2641 IU/L vs. 2391 IU/L, p=0.82) or left ventricular ejection fraction (median;

38% vs. 38%, p=0.99). There was a trend toward shorter duration from symptom onset to

presentation in patients with concave pattern (median; 2-hour vs. 3-hour, p=0.32). Patients with

concave pattern had a significantly lower rate of in-hospital mortality (0% vs. 6%, p=0.03).

Similarly, at 1-year follow-up, patients with concave pattern had significantly lower all-cause

mortality (0% vs. 12%, p=0.001).

Conclusion: Concave pattern ST-segment elevation was significantly associated with lower in-

hospital and 1-year mortalities in patients with first anterior STEMI.

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139

MYOCARDIAL VIABILITY ASSESSMENT PRIOR TO PERCUTANEOUS

CORONARY INTERVENTION FOR CORONARY CHRONIC TOTAL OCCLUSION: A

SYSTEMATIC REVIEW Y.R. Manda, A. Sinha, S. Agrawal, R. Durkin, P. Puleo, C. Sarnoski, J. Shirani

St Lukes University Health Network, Bethlehem, PA, USA.

Background: Patient selection for percutaneous coronary intervention (PCI) of coronary chronic

total occlusion (CTO) has focused on symptoms, lesion characteristics and state of collateral

circulation. Value of myocardial viability assessment has not been well studied in these

anatomically complex lesions.

Methods: Review of literature identified 11 observational (8 prospective, 3 retrospective) studies

that assessed viability before PCI of CTO (n=640) [Table]. These studies were analyzed for

viability parameters and imaging modalities.

Results: Mean age was 63.7 years and 76% were men. Patients were followed up to 12 months. In

earlier studies collateral grade by coronary angiography (CA) (5 studies, n= 157) was used as a

marker of viability with good sensitivity (> 75%) but poor specificity (21% to 65.7%). Transmural

extent of infarction was the primary marker of viability by cardiac magnetic resonance (CMR)

imaging in 6 studies (n=222). Other viability markers included systolic wall thickening,

myocardial blood flow, and contractile reserve. Myocardial perfusion imaging (MPI) was used for

viability assessment in 2 studies (n=321) and an ischemic threshold of >12.5% identified those

with most benefit from CTO PCI.

Conclusion: In absence of prospective studies, demonstration of viability may identify those who

would most benefit from PCI of CTO.

Author Year No. Viability Parameters Results in Relation to Viability

Studies Utilizing Collateral Grade and microvascular integrity by Coronary Angiography

Di Carli 1994 42 Collateral grade & perfusion defects Angiographically visible collaterals sensitive (84%) not specific (21%)

Petronio, 1998 18 Micro vascular integrity & RWT Microvascular integrity correlated with viability

Muehling 2007 30 Collateral grades & perfusion TEI <50%=preserved contractile function in collateral-dependent myocardium

Kumbasar 2007 47 Collateral grades & contractile reserve Collateral grades 2-3 predicts viability (sensitivity 75%, specificity 65.7%)

Chammas 2008 20 Collateral grades & perfusion Collaterals indicative of viability

Studies Utilizing Cardiac Magnetic Resonance imaging

Muehling 2007 30 Collateral grades & perfusion TEI <50%=preserved contractile function in collateral-dependent myocardium

Baks 2006 27 SWT & TEI TEI <25%=likelihood of ↑ SWT on follow up (p<0.001)

Cheng 2008 17 Hyperemic and resting MBF Hyperemic MBF ↑within 24 hours of CTO PCI and persisted at 6 months

(p<0.01)

Fiocchi 2009 23 Diastolic & systolic wall thickness Functional recovery correlated with SWT (p=0.015)

Kirschbaum

2012 72 EDWT, TEI, contractile reserve, SWTur

Contractile reserve+SWTur+TEI better predictive than TEI alone for recovery of

function (p<0.001)

Pujadas 2013 43 Perfusion & TEI Ischemia and DE<50% predicted recovery of segmental perfusion (p,0.001) and

function (p=0.01)

Studies Utilizing Perfusion imaging for viability assessment

Chammas 2008 20 Collateral grades & perfusion Collaterals not protective of inducible ischemia but could preserve viability

Safely 2011 301 Perfusion Ischemia threshold >12.5% of myocardium identified those with most benefit

from CTO PCI

CTO=Chronic total occlusion; DE=Delayed enhancement; EDWT=End diastolic wall thickness); MBF=Myocardial blood flow; PCI=Percutaneous

coronary intervention; RWT=Regional wall thickening; SWT=Systolic wall thickening; SWTur=Systolic wall thickness of unenhanced rim;

TEI=Transmural extent of infarction (by late gadolinium enhancement)

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ROLE OF GALECTIN-3 IN ISCHEMIA/REPERFUSION INJURY S. Al-Salam1, S. Hashmi2

1. College of Medicine & Health Sciences, UAE University, Alain, UAE

2. Agha Khan University, Karachi, Pakistan

Myocardial reperfusion has the potential to salvage the ischemic myocardium after a period of

coronary occlusion. Reperfusion, however, can cause a wide spectrum of deleterious effects.

Galectin-3 (GAL-3), a beta galactoside binding lectin, is closely associated with myocardial

fibrosis and heart failure. We investigated its role in ischemia-reperfusion injuries (IR). C57B6/J

wild type (WT) mice and GAL-3 knockout (KO) mice were used for murine model of Ischemia-

reperfusion in the heart where a period of 30 min ischemia was followed by 24 hours of

reperfusion. There was a significant increase in GAL-3 levels in the left ventricle after IR injury

which signifies an important role for GAL-3 in IR in the heart. Troponin I levels were found to be

significantly higher in GAL-3 KO group than the GAL-3 WT group depicting that GAL-3 is

regulating troponin I levels in the IR model. Antioxidant enzymes Superoxide dismutase,

Glutathione and catalase were found to be significantly raised in the GAL-3 WT IR group as

compared to the GAL-3 KO IR group. We also noticed a more anti-apoptotic bcl-2 and less pro-

apoptotic cleaved caspase-3 and cytochrome c protein expression in GAL-3 WT IR group than in

GAL-3 KO IR group. Our study shows that GAL-3 is associated with an increase in the anti-

oxidant activity in the IR injured myocardium. We can conclude that GAL-3 can interfere with

redox pathways controlling cell survival and death and plays a protective a role in the pathogenesis

of ischemia reperfusion injury in the heart.

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141

NOT ALL ST-SEGMENT CHANGES ARE MYOCARDIAL INJURY:

HYPERCALCEMIA-INDUCED ST-SEGMENT ELEVATION A.O. Strand1, T.T. Aung1, A. Agarwal1,2

1. Wright State University, Dayton, OH, USA

2. VA Medical Center, Dayton, OH, USA

Objectives/Background: While other causes of ST-segment elevation on electrocardiogram (EKG)

than ischemia have been described, hypercalcemia is an etiology that has been rarely documented.

Description: We describe the case of an 83 year old man with coronary artery disease, ischemic

cardiomyopathy with left ventricular ejection fraction of 15%, newly diagnosed multiple myeloma

and other comorbidities who presented with shortness of breath and increased leg swelling,

denying any chest pain. Thorough workup revealed new ST segment elevation in anterior leads

(V1-3) and ST segment depression in lateral leads with subsequent labs showing hypercalcemia

and negative cardiac enzymes. It was thought that the EKG changes were not indicative of cardiac

ischemia and he was treated with fluids, diuretics and zolendronic acid with subsequent resolution

of ST segment changes.

Results/Discussion: ST-segment changes mimicking myocardial ischemia must be taken into

consideration if physical exam and history do not lend itself towards myocardial injury as

unnecessary invasive revascularization procedures have inherent risks. In medical literature, EKG

features of hypercalcemia are described as: absent or shortened ST segment, shortened QT

segment, and lengthened T wave duration. In addition, there have been approximately 26 reported

cases of hypercalcemia leading to ST-elevation, mostly localized to anterior leads (V1-3). The

physiologic mechanism of these changes is unknown. Many of these cases note the ST-elevation

due to hypercalcemia is likely more common than currently documented in medical literature.

Conclusion: Our patient’s ST segment changes mimicking myocardial injury on EKG were due

to hypercalcemia. Further vigilance is required to determine if this really is a relatively common

cause of ST-elevation mimicking ischemia.

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ACUTE CORONARY SYNDROMES, INTERVENTIONAL THERAPIES

142

PRIMARY PERCUTANEOUS CORONARY INTERVENTION (PPCI) IN

OCTOGENERIANS: CLINICAL CHARACTERISTICS AND OUTCOMES IN AN

AUSTRALIAN REGIONAL SETTING S.M. Hayman1,2, Y. Chacko1,2, S. Butterly1, A. Willson1,2, R. Poulter1, P. Larsen1,

C. Thompson1, D. Colburn1, K. Lau1,2, M. Johnson1

1. Nambour General Hospital, Nambour, QLD, Australia

2. University of Queensland, Brisbane, QLD, Australia

Background: The Sunshine Coast Hospital and Health Service (SCHHS), Queensland, Australia

began a PPCI service in 2012. The region has a large elderly population with proportions of >65

year old residents projected to increase from 18% in 2011 to 21.8% by 2026 with >85 year olds

trebling over this period.

Aim: To compare PPCI characteristics and outcomes in the elderly (>80yrs) verses non-elderly

(<80yrs) STEMI population treated within SCHHS.

Methods & Results: Data on all PPCI patients since commencement to January 2015 were collected

prospectively. Of 405 PPCI, 61(15%) were elderly. Compared to the younger cohort, the elderly

were more likely to be female (38%v22%, p=0.01), had previous CABG (10%v3%, p=0.002), and

have hypertension (67%v44%, p=0.002). Elderly patients had marginally longer (non-significant)

median [interquartile range] door-to-balloon times (DTBT) (50 [63] v 45 [50] mins, p=0.27), were

less likely to receive ticagrelor (48%v62%, p=0.13) or IIb/IIIa inhibitor (38%v56%, p=0.013) and

more likely to receive bare metal stents (36%v20%) or no stent (26%v23%). Thirty-day mortality

in the elderly cohort was higher (18%v3%, p<0.001). Of the eleven elderly deaths, four had cardiac

arrest, three arrived intubated and ventilated, three had LMCA culprit and only five received PCI.

For those receiving PCI who subsequently died, median DTBT was 106 [99] mins.

Conclusion: Octogenarians represent a substantial proportion of referrals for primary PCI and is

expected to increase. Timely PPCI is feasible in this inherently high-risk group however mortality

is higher compared to a younger cohort.

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143

LARGEST REPORTED SINGLE OPERATOR PERCLOSE CLOSURE DEVICE

EXPERIENCE WITH VERY LOW COMPLICATIONS K. Kang, G. Kang

UPMC Hamot Hospital, Erie, PA, USA

Background: Femoral artery is the most common access site in cardiovascular procedures in US.

Radial access is recommended as an option for both early patient ambulation and lower

complication risk. However, the need for a switch in practice to radial access may not be necessary

for physicians with large experience with femoral access who always do their own access stick

and closure rather than have a trainee attempt it.

Methods: Our hospital participates in the American College of Cardiology National

Cardiovascular Data Registry (ACC NCDR) and we analyzed the data on patients who underwent

procedures from 01/01/2006 to 12/31/2014 by a single operator. Ambulation time is ordered as 2

hours for Perclose patients. Data were recorded by independent hospital staff. All the definitions

of complications are ACC NCDR based.

Results: The single operator who is American Board of Internal Medicine Interventional

Cardiology certified, performed procedures on 6,726 total patients and of these 6,218 were femoral

access with Perclose device used on 4,995 (80.3%) patients. No patients are excluded from this

analysis of patients with Perclose and the results are as below. Mortality 0.4%, Bleeding 0.4%,

Dissection 0.1%, Thrombosis 0.5%, Occlusion 0%, Pseudoaneurysm 0%, Embolism 0% and

Fistula 0%. No infection was noted. The total data on 6,726 patients also showed the above

complications to be below 1% for each category.

Conclusions: Femoral Access with Perclose is extremely safe in the hands of experienced

operators who do their own initial stick and closure device placement. Hence, experienced

physicians with excellent femoral outcomes using the Perclose Closure Device may not switch

their practice to radial access approach.

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144

MORBIDLY OBESE PATIENTS GET EXCELLENT OUTCOMES WITH FEMORAL

ACCESS WHEN ACCESS IS OBTAINED BY EXPERIENCED OPERATORS K.S. Kang1, A. Kapoor2, G.S. Kang1

1. UPMC Hamot Hospital, Erie, PA, USA

2. Saba University School of Medicine, Devens, MA, USA

Objectives: During vascular procedures, radial access is preferred over the femoral access in the

morbidly obese patients per American College of Cardiology (ACC) guidelines but the guidelines

do not acknowledge operator experience. We hypothesize that experienced operators get excellent

femoral outcomes in high-risk groups like the morbidly obese. Background: Only American Board

of Internal Medicine (ABIM) Interventional Board certified operators attempt arterial access in

our hospital. We defined an "experienced operator" as certified in ABIM. Excellent outcomes are

defined as access site complication rates of less than or equal to 1% based on outcomes considered

favorable in prior radial access studies. In prior studies favoring radial access, it was not required

for access attempts to be made only by an experienced operator. Femoral artery being an end-

artery be less forgiving than radial artery when thrombosed.

Methods: All patients presenting between 01/01/2006 and 10/31/2014 that had femoral access and

a BMI greater than 40 were included in our study. The total number of patients was 3179. All data

reported in this study are taken from the ACC/National Cardiovascular Data Registry

(ACC/NCDR). ACC defined the variables evaluated by us, which are available at

http://www.ncdr.com.

Results: Our results reveal that there was low overall mortality (<0.6%) and no access site

infection. Vascular complications included bleeding (0.5%), thrombosis (0.3%), dissections

(0.1%), occlusions (0.0%), pseudo-aneurysms (0.1%), emboli (0.0%) and fistulae (0.0%).

Conclusions: Experienced operators obtain excellent outcomes in morbidly obese patients from

the femoral approach and uniform preference of radial access may not be necessary.

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145

TRANSCATHETER REPAIR OF A RADIAL ARTERIOVENOUS FISTULA AFTER

CARDIAC CATHETERIZATION USING A COVERED STENT D. Khurana, J. Raza, R. Rosen, M. Kim, V.P. Singh

Lenox Hill Hospital, New York, NY, USA

Introduction: Arteriovenous fistulas after cardiac catheterization using radial approach are

extremely rare. We report a case of arteriovenous fistula following transradial access which was

repaired successfully using a covered stent.

Case Report: A 55-year old female underwent coronary angiography for non-ST elevation MI.

Patient had a normal Allen’s test prior to procedure. The right radial artery was cannulated for

access using a 5F radial sheath which was removed after completion of procedure. A radial band

was applied for hemostasis and removed 2 hours later with no evidence of bleeding or hematoma.

On follow-up visit, patient complained of pain in her right upper extremity (RUE) and had a

palpable thrill on examination. MRA of RUE revealed radial AV fistula with rapid filling and

opacification of the veins near the radial artery. RUE angiogram was performed in the cardiac

catheterization lab using impulse diagnostic catheter. It demonstrated arteriovenous fistula

involving distal radial artery. A 110 cm 7F Shuttle sheath was then advanced over a supracore

wire, followed by a 125cm Vertebral catheter, advanced distally across the fistula origin.

Superselective angiogram was performed confirming flow into the radial artery distal to the AV

fistula. A Viabahn 6mm x 5cm covered stent was advanced over the Supracore wire and deployed

across the fistula origin. Post-dilation with a 5mm x 40mm FoxCross balloon was performed. Final

angiography demonstrated excellent flow through the stent with no residual fistulous

communication. Patient tolerated the procedure well and experienced complete resolution of

symptoms.

Conclusion: Transcatheter repair of radialarteriovenous fistulas using covered stents is a safe and

effective method. In a select patient population, endovascular covered stents provide a less

invasive treatment modality compared to surgery.

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146

COMPARISON OF MANUAL COMPRESSION AND ARTERIAL CLOSURE DEVICE

FOLLOWING PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH

STEMI USING BARC CLASSIFICATION M. Aradhya, H. Vefali, J.P. Perdomo Rodriguez, Y. Manda, S. Agrawal, A. Singh,

A. Sinha, J. Shirani


Background: Bleeding complications are associated with increased risk of adverse outcomes

following percutaneous coronary intervention (PCI). A meta-analysis of 16 studies had suggested

a reduction in vascular complications with the use of Angio-Seal closure device compared to

manual compression (MC). However, safety comparison between studies was difficult due to

substantial heterogeneity in defining significant bleeding. We compared bleeding complications

after PCI between Angio-seal and MC in the setting of primary PCI for STEMI, using the BARC

(Bleeding Academic Research Consortium) bleeding definitions.

Methods: Retrospective chart review and data collection was performed on consecutive patients

who underwent primary PCI through femoral approach for STEMI between September 2011 and

June 2013. The bleeding complications were compared between MC and vascular closure device

(VCD) using BARC classification.

Results: Data was obtained in 190 patients (age 64±13 years); 124 (66%) men. Two patients were

excluded due to insertion of an intra-aortic balloon pump. Of the remaining 188 patients, 50

(26.5%) had MC, 108 (57.3%) had Angio-Seal and 30 (14%) had Perclose proglide VCDs.

Bleeding complications were compared between the Angio-Seal group (n=108) and MC (n=50)

group based on the BARC classification. There were 10 patients with type 1 bleeding and 15

patients with type 2 bleeding in total and 133 had no bleeding. Statistical analysis indicated no

relationship between the technique of hemostasis used and the presence or severity of bleeding

complications (p =0.56).

Conclusions: When BARC classification is used to define vascular access site bleeding

complications, MC is as effective as Angio-Seal in providing hemostasis following femoral

approach to primary PCI in the setting of acute STEMI.

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147

QUALITY AT THE CATHLAB: CORONARY REINTERVENTION RATE AT 30 DAYS J.M. Telayna, J.M.H. Telayna, R.A. Costantini

Hospital Universitario Austral, Buenos Aires, Argentina

Introduction: Post coronary angioplasty readmissions counts from 9 - 48%, many of them being

avoidable.

Objective: To evaluate coronary reintervention rates in patients admitted with chest pain within 30

days after coronary angioplasty (PTCA)

Materials and methods: Among January 2005 to December 2014, 2022 PTCA were performed.

Patients (pts) deceased during index hospitalization and those with acute coronary syndrome as an

epiphenomenon were excluded, leaving the final number at 1931 pts. Within 30 days, 160 of them

required hospitalization after PTCA (8.2%) to evaluate symptomatic recurrence. 54 (34%) pts

underwent new angiography while 106 (66%) pts went through medical treatment optimization.

Of those pts with renewed angiography, 20 pts (group A) had new PTCA, whereas 34 pts (group

B) had no new angiographic findings. Baseline characteristics from group A and B n(%)

respectively: mean age 63.23±11 vs 61.1±10.8 years; diabetes 11(55) vs 10(29) p=0.06; ACS

15(75) vs 23(67); LVF average 58.7±5.6 vs 63.2±17.9; bifurcation lesions 3(15) vs 4(12); chronic

coronary occlusion 2(10) vs 0; more than 33 mm of stent 16(80) vs 20(59); re-angina and new

changes in ECG 6(30) vs 0 p=<0.001; re-angina and positive troponin 2(10) vs 9(26); re-angina

with new changes in ECG and troponin positive 5(25) vs 1(3) p=0.02; intracoronary thrombosis

6(30) vs 0 p=<0.001.

Results: From 1931 angioplasties performed, global reintervention rate was 1.03%. Then, 2(10) vs

1(3) pts had clinically relevant myocardial infarction (p=0.5); and 1 (5) vs 0 (p=0.3) had

cardiovascular death. Reinterventions were because of: 1) subacute coronary occlusion in 6 (30)

vs 0; 2) another lesion or another vessel in 14 (70) vs 0.

Conclusion: The rate of coronary reinterventions within 30 days post-angioplasty in patients with

new episode of chest pain was low. The dyad of chest pain and new ECG changes was the best

determined of intracoronary thrombosis.

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148

USE OF IMPELLA CP AS AN ADJUNCT TO BALLOON AORTIC VALVULOPLASTY

AND STENTING OF UNPROTECTED LM K.N. Mezue1, H.S. Rammohan2, A.M. Dias2, S. Patnaik1, C.F. Witzke2

1. Einstein Medical Center, Philadelphia, PA, USA

2. Einstein Institute for Heart and Vascular Health, Einstein Medical Center, Philadelphia, PA,

USA

Background: In an aging population, the occurrence of co-existent aortic stenosis and left main

(LM) or equivalent coronary disease poses a major challenge to patients and clinicians, especially

when these patients are not surgical candidates due to multiple co-morbid conditions. Alternative

options need to be considered.

Case: 86 year old female admitted with chest pain. She was ruled in for non-ST elevation MI based

on dynamic EKG changes with ST depressions in V4-V6 and peak troponin-I level of 4.47.

Echocardiogram revealed severe biventricular dysfunction with LVEF of 30% and severe aortic

stenosis with AVA of 0.6cm2. Due to co-morbidities she was deemed not to be a surgical candidate

and a percutaneous approach was offered. Catheterization Findings & Intervention: The left main

and right coronary artery revealed >90% disease. An Impella CP device was retrogradely advanced

into the left ventricle over the 0.035”-280 cm Amplatz stiff wire. The left main lesion was crossed

using 0.014”-180cm whisper wire. Laser atherectomy and stenting was performed with 4.0 x12

mm Promus stent. Stenting of the distal and proximal segment of the RCA was performed using a

6 French guide liner; a 3.0 x 24 mm and 4.0 x 12 mm Promus stents were deployed respectively.

Percutaneous aortic balloon valvuloplasty was performed successfully under rapid pacing by using

a 16 x 5 cm Z-Med balloon.

Conclusion: Unprotected left main coronary artery stenting and sequential balloon aortic

valvuloplasty for critical aortic stenosis with Impella device support is a viable option in high risk

patients for surgery. The combined procedure serves as a bridge to TAVR or palliation.

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149

REDUCTION IN THE USE OF DRUG ELUTING STENTS AFTER INTIAL

INCREASING TREND IN THE SETTING OF STEMI IN THE UNITED STATES M.R. Movahed, M Hashemzadeh, M. Hashemzadeh

CareMore, University of Arizona, Long Beach VA Health Care System, Tucson, AZ, USA

Background: Drug eluting stents are increasingly utilized during intervention. The goal of this

study was to evaluate this trend in in the United States using inpatients data. Method: The

Nationwide Inpatient Sample (NIS) database was utilized to calculate the age-adjusted rate for

drug eluting stent use from 2003-2007 in the setting of STEMI in the United State using ICD-9

coding.

Results: We found that age adjusted rate for the use of drug eluting stents in the United States

initially increased from 2003 to highest level in 2006 with gradual reduction in 2007. (Age adjusted

rate for the use of drug eluting stent was 8.9 per 100,000 in 2003. It increased to highest trend of

34.6 per 100.000 in 2006 with reduction to 20.3 per 100,000 in 2007).

Conclusion: Initial higher utilization rate of drug eluting stent in the setting of STEMI did not

persist. The cause of this lower trend in 2007 is not known but is probably related to the fear of

higher stent thrombosis rate.

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PATHOGENESIS, DIAGNOSIS AND TREATMENT OF AORTIC ANEURYSMS AND PERIPHERAL ARTERY DISEASE

150

PRDX II DEFICIENCY INSTIGATES THE DEVELOPMENT OF ANGIOTENSIN II-

INDUCED ABDOMINAL AORTIC ANEURYSMS N.Y. Ko1, J.G. Park1,2, S.J. Jeong1, S. Kim1, G.T. Oh1

1. Department of Life Sciences, Ewha Womans University, Seoul, Republic of Korea

2. Department of Pathology and Laboratory Medicine, New York, NY, USA

With population aging, abdominal aortic aneurysms are becoming common vascular disorders.

AAAs exhibit progressive dilations of the abdominal aorta, and rupture of it is often a lethal event.

Although it is well documented that inflammation and oxidative stress are pathogenic mediators

of AAA, the molecules that could be therapeutic targets are not well characterized. Peroxiredoxin

II is one of major isoforms of peroxiredoxin, a critical antioxidant enzyme, and exhibit higher

affinity toward low concentrations of hydrogen peroxide. The purpose of this study is to determine

whether PrdxII contributed to the development of AAA. In aortas from aortic aneurysm patients,

there was a marked increase in expression level of PrdxII. We confirmed it in mouse AAA model,

infusing angiotensin II via subcutaneous os motic pumps. To further investigate the role of PrdxII

in AAA formation, we established Prdx II KO mice. Compared with wild type control,

subcutaneous infusion of Ang II markedly increased the incidence of AAA in PrdxII KO mice.

PrdxII deficiency enhanced AngII induced changes in overall abdominal aorta morphology and

the increase in aorta diameter. High frequency ultrasound images of abdominal aorta, which is

taken at the level of the suprarenal aorta in every week after AngII infusion, also showed more

advanced dilations of abdominal aorta at earlier time point in PrdxII KO mice. Correspondingly,

SMA positive cells and elastic lamina degradations are elevated in aneurysm sections from PrdxII

KO mice. In addition, when comparing AngII treated WT mice, aortas from AngII infused PrdxII

KO mice displayed increased immune cell infiltration and significantly upexpression of

proinflammoty cytokines in AAA. These results indicate that PrdxII has a pivotal role in

modulating of AngII induced AAA. With mechanistic further studies, our research might suggest

PrdxII as a potential therapeutic target for prevention of AAA.

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151

CO2-ENRICHED WATER BATH AS A NOVEL THERAPY FOR PERIPHERAL

VASCULAR DISEASE

N.S. Dhalla

ICS, St. Boniface Hospital Research, Univ. of Manitoba

Peripheral artery disease (PAD) is a major health problem whereby narrowed arteries reduce blood

flow to the ischemic limbs. We investigated the effects of CO2-enriched water bath (CEWB)

therapy on blood flow in the ischemic hind limb. The femoral artery was occluded in rats to induce

PAD and the animals were treated with or without CEWB at 37°C for 4 weeks (20 min/day; 5

days/week) starting one week after artery occlusion. CEWB was prepared by using Carbothera

(Mitsubishi Rayon Engineering, Tokyo). Peaks, mean and minimal blood flows, as measured by

Pulse Wave Doppler Ultrasound technique, were not detected in the untreated ischemic hind limb

of animals due to arterial ligation. However, blood flow values were about 50% of the control

upon treatment with CEWB; 67% of the ligated animals showed positive blood flow by CO2

treatment. Morphological examination of the treated ischemic skeletal muscle revealed a 3-fold

increase in small artery numbers indicating the formation of new blood vessels. Although plasma

triglycerides decreased and plasma NO concentration increased in ischemic animals, CEWB

treatment produced no effects on these parameters. It is suggested that beneficial action of CO2

therapy on blood flow to hind limb may be due to the development of angiogenesis in the ischemic

skeletal muscle. (Infrastructure support for this study was provided by the St. Boniface Hospital

Foundation)

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152

WHOLE EXOME SEQUENCING FOR THORACIC AORTIC ANEURYSM:

THE FUTURE IS HERE

J.A. Elefteriades

Yale University School of Medicine, New Haven, CT, USA

Background: Convincing evidence is accumulating that genetics play an important etiologic role

in thoracic aortic aneurysm and dissection (TAAD). Multiple genes have been found to cause

syndromic and familial TAAD. The current study evaluates the impact of genetic testing via whole

exome sequencing (WES) for a panel of genes associated with TAAD as a clinical test performed

at a specialized aortic center.

Methods: WES was offered as an ongoing clinical test to 188 patients (mean age 59.2±14.8 years,

range 13-85, 131 males (69.7%)) with TAAD. Thirty-four patients were declined testing for

insurance reasons. DNA was extracted from saliva samples collected in Oragene kits. DNA exonic

fragments were sequenced on the Illumina HiSeq platform. The resulting sequence was analyzed

for single nucleotide variants and small insertions and deletions differing from the reference

genome (Human Genome 19, HG19). To date, genetic results were available for 102 patients

(66.2%).

Results: The panel of tested genes is presented in Figure 1. Three patients (2.9%) had a deleterious

mutation identified in the FBN1, COL5A1, and MYLK genes. Twenty patients (19.6%) had

suspicious variants of unknown significance (previously unreported) in one or more of these genes:

FBN1 (n=5), MYH11 (n=4), ACTA2 (n=2), COL1A1 (n=2), FLNA (n=2), TGFBR1 (n=2),

COL3A1 (n=1), COL5A1 (n=1), COL5A2 (n=1), NOTCH1 (n=1), PRKG1 (n= 1), and TGFBR3

(n=1). Identified mutations had implications for clinical management. Seventy-three patients

(71.6%) had no medically important genetic alterations.

Conclusion: Routine genetic screening of patients with TAAD provides important information that

enables genetically personalized care and permits identification of novel mutations responsible for

aortic pathology.

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153

WHAT DIABETES MELLITUS HAS TAUGHT US ABOUT POTENTIAL

TREATMENTS FOR SMALL ABDOMINAL AORTIC ANEURYSMS S.D. Gertz1, L. Gavish1, Y. Mintz2, R. Beeri3, C. Rubinstein4, L.Y. Gavish1,

Y. Berlatzky4, L. Appelbaum5, D. Gilon3

1. Institute for Medical Research (IMRIC), The Hebrew University--Hadassah Medical School,

Jerusalem, Israel

2. Department of Surgery, Hadassah University Hospital, Jerusalem, Israel

3. Department of Cardiology, Hadassah University Hospital, Jerusalem, Israel

4. Department of Vascular Surgery, Hadassah University Hospital, Jerusalem, Israel

5. Department of Radiology, Hadassah University Hospital, Jerusalem, Israel

Increased detection of abdominal aortic aneurysm (AAA) at early stages of growth (more than

80% of those diagnosed now are less than 3.5 cm maximum diameter), and the high rate of severe

complications of urgent, open abdomen or endovascular surgical treatment have emphasized the

need for less invasive strategies that target the pathogenetic mechanisms of progression and

rupture. In sharp contrast to hypercholesterolemia, diabetes mellitus (DM) is negatively associated

with AAA in experimental animal models and in epidemiological studies in humans. Whereas

hypercholesterolemia favors an increased proteolytic state in the arterial wall, diabetes, through

increased glycation of protein precursors and increased advanced glycation end products,

facilitates matrix protein synthesis and increases covalent bonding of matrix proteins, rendering

the wall less prone to proteolysis, decreasing the likelihood of aneurysmal dilatation and rupture.

Recent studies from our laboratory have shown that Low Level laser (LLL) photobiomodulation,

in the visible to near infrared range [780 nm] of the electromagnetic spectrum, used widely

clinically for reducing pain and increasing wound healing, inhibits the development and

progression of AAA in the angiotensin-II-infused, apolipoprotein-E-deficient mouse. The

mechanism for this effect involves upregulation of collagen-rich fibrous matrix repair of

transmedial defects in the aortic wall in the vicinity of aortic branch orifices. Reinforcement of

the extracellular matrix in the aortic wall also explains the negative association between DM and

AAA even though the underlying cellular mechanisms are different. In this talk, we discuss the

use of minimally invasive photobiomodulation, and other options, for mechanism-based targeting

and management of small, progressing aneurysms that are refractory to risk factor modification

and pharmacological therapy in order to save the patient from the frequently severe consequences

of urgent, obligatory, surgical or endovascular intervention.

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154

STRATEGIES FOR PREVENTION OF CARDIOVASCULAR EVENTS IN PATIENTS

WITH POLYVASCULAR DISEASE T. Tomaru1, T. Matsubara2, E. Matsubara2, T. Ariyama3

1. Toho University Sakura Hospital, Japan

2. Tokyo University Hospital, Japan

3. Toho University Department of Pharmacology, Japan

Patients with severe carotid arterial sclerosis or those with polyvascular disease (PVD ) are at high

risk for cardiovascular events.

Ultrasonography(US) is very useful for detection of PVD and we investigated usefulness of US

and prognosis of patients with PVD or those with severe carotid arteriosclerosis. Carotid arterial

sclerosis was evaluated by carotid US and plaque score (PS) was calculated. PS was summation

of maximum thickness of each plaque and graded as follows: severe (10≤PS ), moderate

(5≤PS <10) and mild (PS<5). Out of 2428 patients who underwent US in 2010, severe

arteriosclerosis was observed in 602 patients. 102 of them had PVD. In most of patients with PVD,

treatment of diseased major vessels was done. Diagnosis of PVD was based on exercise test, US,

coronary angiography. MRI. In 380 patients with severe carotid sclerosis, antiplatelet drug was

administered. Most of patients had more than 2 risk factors for arteriosclerosis. During 3 year

follow up of patients with severe carotid sclerosis without significant carotid stenosis, cerebral

infarction (CI) occurred in 10 (4 with antiplatelet) and acute myocardial infarction (AMI) occurred

in 6 (3 with antiplatelet). In 1258 patients with mild carotid arteriosclerosis, CI occurred in 12 and

AMI occurred in 7 patients. In 24 cases with severe stenosis, CEA was done and restenosis was

not observed. There was no significant difference in development of CI or AMI between severe

and mild carotid arteriosclerosis. In 78 cases with PAD, PTA with stenting was done in 32 and

restenosis was observed in 5. If severe carotid, coronary or peripheral arterial stenosis is treated,

cardiovascular events in patients with PVD can be prevented in most of patients of our hospital.

Diagnosis of carotid arterial sclerosis by US and treatment with antiplatelet drug are useful for

prevention of cardiovascular event in high risk patients.

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155

DIAGNOSTIC TRICKS AND TIMELY TREATMENT OF AORTIC INTRAMURAL

HEMATOMA H.K. Reddy1, R.C. Komatireddy2, R.K. Sharma3, D.J. Voelker3

1. St. Louis University Medical School, St. Louis, MO, USA

2. University of California, San Diego, CA, USA

3. University of Arkansas for Medical Sciences, Little Rock, AR, USA

Aortic intramural hematoma is a variant of acute aortic syndrome with a presentation similar to

that of acute aortic dissection but difficult to make a timely diagnosis. This entity may be easily

missed because of the absence of the intimal flap often seen in classical dissection. An intramural

hematoma is formed from medial hemorrhage from rupture of the vasa vasorum and the

subsequent weakening of the aortic wall. In spite of the subtlety of this condition, it is critical to

make a prompt diagnosis because of the high mortality rate of 21% associated with it. Some

specific CT findings on the unenhanced and contrast-enhanced CT axial images are listed below

1. Intimal areas of calcification in a curvilinear configuration.2. An enlarged aortic diameter and

crescentic, eccentric hyperattenuating area of the thickened aortic wall (60-70 HU) Conventional

aortic angiogram may not detect intramural hematoma since the appearance of intimal flap and

double lumen is absent. CT and TEE show circumferential or crescentic aortic wall thickening of

more than 7mm.Therefore, prompt and accurate detection of aortic intramural hematomas is

critical to providing appropriate therapy. Timely surgical repair of ascending aortic intramural

hematoma is needed whereas medical therapy with a good control of blood pressure may be

pursued in patients with descending aortic intramural hematoma.

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156

PATIENT QUALITY OF LIFE FOR TISSUE AND MECHANICAL VALVES AFTER

COMPOSITE AORTIC ROOT REPLACEMENT A.A. Repack, B.A. Ziganshin, J.A. Elefteriades, S. Mukherjee

Aortic Institute at Yale-New Haven Hospital, Yale University School of Medicine, New Haven,

CT, USA

Objective: To assess whether postoperative quality of life for composite aortic root replacement

patients differs based on the use of mechanical valves or tissue valves. Background: It is presumed

that biological valves provide higher quality of life than mechanical. We examined this

preconception in the specific setting of aortic root replacement.

Methods: 146 consecutive patients who underwent composite aortic root replacement at our

institution from January 2010 to April 2014 with a tissue valve (34.9%, n=51) or a mechanical

valve conduit (65.1%, n=95). Patient perceived quality of life was measured using the Short Form

36v2 Health Survey augmented by a series of supplemental questions to further evaluate valve

specific differences. Survey participation included 76.5% (39/51) of patients with tissue valves,

and 86.3% (82/95) of patients with mechanical valves.

Results: No significant differences were found between the tissue and mechanical valve groups

for any quality of life aspects scored by the SF-36v2 survey. All 8 domains and 2 summary scales

comprising the evaluation were above national norms calculated using gender and age matched,

norm-based scoring. The supplemental questions indicated patient satisfaction with each valve

type. In the mechanical valve group, 90.2% (74/82) reported the audible valve click was not

troublesome, 85.4% (70/82) reported taking a blood thinner regularly did not affect daily life, and

81.7% (67/82) of patients reported blood testing for anticoagulation therapy was not troublesome.

Conclusions: Receiving a tissue or mechanical valve does not directly affect postoperative quality

of life in composite graft aortic root replacement. Answers to supplemental questions suggest

previous concerns with mechanical valves do not affect patients in the commonly accepted

negative manner. The preconception of heavy quality of life burden for mechanical composite

grafts is contradicted by this study.

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157

LONG-TERM SURVIVAL IN PATIENTS WITH CONTRALATERAL CAROTID

OCCLUSION AFTER ENDARTERECTOMY. A COMPARATIVE STUDY C. Rubio-Taboada, J.L. Duran-Mariño, J.M. Garcia-Colodro

Department of Vascular Surgery, University Hospital Lugo, Spain

Severe carotid stenosis is typically treated by carotid endarterectomy , (CEA), but there’s no

agreement about the safety of this procedure in patients with contralateral carotid occlusion (CCO).

Objective: The aim of the present work is to assess how the CCO affect 30-day outcome and the

long-term survival and to compare to those without CCO.

Methods: We reviewed medical records of 434 patients who underwent CEA, 394 as group I and

40 with CCO (group II).

Results: The mean age was 72 and 71,35 years respectively. The mortality following all CEA was

1,6% (1,7% vs 0%; p=0,395). The overall stroke rate was 3,5% (3,8% vs 0%; p=0,209). The

transitory ischemic attack rate was 1,38% (1,26% vs 2,5%; p=0,370). At mean follow-up of

75,49±47,5 months (group I) and 72,72±49,9 months (group II), 157 additional deaths were

identified in group I and 13 deaths in group II (p=NS). Long-term survival curves did not show

statistical difference for both groups ( p = 0,514 ). Overall 1, 5, 10 and 15 -year survivals were for

group I 92.2%, 78.8%, 49.8% ,34.8% and for group II were 97.5%, 79%, 50.8% ,42.3%

respectively.

Conclusion: Patients who have to undergo CEA with CCO seem not to have an increased risk for

perioperative incidence of stroke and death. These patients have an excellent cumulative 15-year

survival.

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170


CARDIOVASCULAR DISEASE AND CARDIOPROTECTION IN DIABETES AND METABOLIC SYNDROME

158

MITOCHONDRIAL QUALITY CONTROL IN TYPE 1 DIABETIC HEART Q. Liang, S. Kobayashi, A. Kaminaris, Y. Huang

NYIT College of Osteopathic Medicine, Old Westbury, NY, USA

Mitochondrial dysfunction and reactive oxygen species (ROS) are critical to diabetic heart

damage. However, antioxidant therapies have failed to reduce heart failure in clinical trials,

underscoring the need to develop new therapeutic strategies. A healthy pool of mitochondria is

maintained through a number of quality control mechanisms including mitochondrial autophagy

known as mitophagy which degrades dysfunctional mitochondrial fragments that are segregated

by the fission process. The present study investigated the functional roles of mitophagy and

mitochondrial fission in high glucose (HG)-treated cardiomyocytes and in type 1 diabetic heart.

Mitochondria in the diabetic heart appeared small and spherical, suggesting increased

mitochondrial fragmentation. Meanwhile, mitophagy flux was markedly diminished in the diabetic

heart as determined by a novel dual fluorescent mitophagy reporter in the absence and presence of

the lysosomal protease inhibitors E64d and Pepstatin A. Human diabetic hearts also showed

reduced markers for mitophagy. Similarly, HG increased mitochondrial fragmentation and

inhibited mitophagy in cultured cardiomyocytes, which was accompanied by increased cell death.

These observations demonstrate a mismatch or uncoupling between mitochondrial fission and

mitophagy in the diabetic heart and in HG-treated cardiomyocytes, which may contribute to

diabetic cardiac injury. Indeed, overexpression of the E3 ligase Parkin increased mitophagy flux

and diminished HG toxicity; while parkin knockdown had the opposite effects as measured by the

levels of ROS generation, oxidative injury and cardiomyocyte death. Further, overexpression of

the fission factor Drp1 increased mitochondrial fragmentation and reduced HG-induced

cardiomyocyte injury, while Drp1 knockdown inhibited fission, predisposing cells to high glucose

toxicity. Together, these findings suggested that whereas the HG-induced inhibition of mitophagy

is detrimental, the increased mitochondrial fragmentation appears to be adaptive that limits HG

cardiotoxicity. Studies are underway to determine if these results also hold true in the hearts of

type 1 diabetic mice.

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159

TARGETING MOLECULAR PATHWAYS IN DIABETES ASSOCIATED

CARDIOVASCULAR DISEASE D. Mundil*1, A. Cameron-Vendrig*1, E.A. Shikatani1, A. Reheman3, M.A. Siraj2,

A. Momen2, T. Afroze2, P.H. Backx1, H. Ni3, M. Husain2

1. University of Toronto, Toronto, ON, Canada

2. Toronto General Research Institute, Toronto, ON, Canada

3. St. Michael's Hospital, Toronto, ON, Canada *Equal contribution

Background: Mechanisms underlying the ability of glucagon-like peptide-1 (GLP-1) to prevent

myocardial ischemic injury, and reduce cardiovascular event rates in short-term studies of diabetic

subjects receiving GLP-1-targeted therapies are not known.

Methods and Results: Here we show that cardioprotective effects of a metabolite of GLP-1, namely

GLP-1(28-36), are mediated by soluble adenylyl cyclase Adcy10 (sAC) expressed in mouse

coronary artery smooth muscle cells (caSMC). Ex vivo and in vivo mouse models of ischemia-

reperfusion injury and myocardial infarction respectively revealed that GLP-1(28-36) was as

cardioprotective as GLP-1, with its effect abolished by scrambling its amino-acid sequence.

Pharmacological inhibitors, siRNA and sAC-null mice demonstrated that GLP-1(28-36) acts

directly on human and mouse caSMC, resulting in sAC-dependent cytoprotection from oxidative

stress injury. Next, we cloned full-length GLP-1 receptor (GLP-1R) mRNA from a human

megakaryocyte cell line (MEG-01), and found expression levels of GLP-1R in MEG-01 to be less

than pancreas but more than lung. GLP-1 and the GLP-1R agonist exenatide elicited a cAMP

response in MEG-01 cells, and an inhibitory effect on thrombin-stimulated aggregation of human

and mouse platelets. Incubation with exenatide also inhibited thrombus formation in perfusion

chamber experiments with whole blood. In a cremaster artery laser injury model, exenatide

inhibited thrombus formation in normoglycemic and hyperglycemic mice in vivo. Thrombus

formation was greater in mice transplanted with bone marrow lacking a functional GLP-1R (Glp1r-

/-), as compared to wild-type bone marrow. However, anti-thrombotic effects of exenatide were

only partly lost in mice transplanted with bone marrow from Glp1r-/- mice.

Conclusions: GLP-1(28-36) represents a new small peptide that targets a novel molecular (sAC)

and cellular (caSMC) pathway for the treatment of myocardial ischemic injury. Inhibition of

platelet aggregation and thrombus formation by GLP-1R agonists represent a potential mechanism

for reduced atherothrombotic events in subjects treated with these agents.

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160

INHIBITION OF PYRUVATE DEHYDROGENASE KINASE DECREASES THE

SEVERITY OF HEART FAILURE

G.D. Lopaschuk

University of Alberta, Edmonton, Alberta, Canada

In heart failure, changes in cardiac mitochondrial energy metabolism contribute to this contractile

dysfunction and to a decrease in cardiac efficiency. The failing heart has defects in energy

metabolic processes that compromise ATP production necessary to maintain contractile function.

Normal oxidative phosphorylation is impaired in the failing heart, oxygen consumption is

depressed, and the heart has compromised ATP production. With reduced oxidative

phosphorylation, the heart increases its reliance on the highly inefficient process of ATP

generation via glycolysis (glucose metabolism occurring outside of the mitochondria). Alterations

in energy substrate metabolism accompanying heart failure are complex, and are partly dependent

on the stage/severity of the syndrome. However, an elevation in glycolytic rates in relation to

glucose oxidation in the failing heart is a consistent finding. We showed an increased uncoupling

of glycolysis from glucose oxidation, accompanied by an enhanced H+ production and decreased

efficiency in mouse and rat hearts subjected to permanent myocardial infarction. Studies involving

heart failure secondary to pressure overload also show a depressed overall oxidative metabolism,

as well as a decrease in glucose oxidation. We have shown that heart failure secondary to an

abdominal aortic constriction, a transverse aortic constriction, or Ang II infusion in mice inhibits

cardiac glucose oxidation. Pharmacological stimulation of glucose oxidation in both rat and mouse

hearts improves overall cardiac energetic and cardiac function. In the failing heart, a decrease in

pyruvate dehydrogenase (PDH) activity (the rate-limiting enzyme involved in glucose oxidation),

and an increase in PDH kinase (PDK) expression (which phosphorylates and inhibits PDH) occurs.

Genetic deletion of PDK can prevent this decrease in glucose oxidation in the failing heart, and is

associated with improved cardiac function. This supports the concept that inhibition of cardiac

glucose oxidation may be a promising approach to treat heart failure.

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161

ROLE OF MITOCHONDRIAL OXIDATIVE STRESS IN GLUCOSE TOLERANCE,

INSULIN RESISTANCE, AND CARDIAC DIASTOLIC DYSFUNCTION

J. Chung1,2, E.M. Jeong3,4,5, H. Liu3,4,5, Y. Go1, S. Gladstein4, A. Farzaneh-Far1,

E.D. Lewandowski2,6, S.C. Dudley3,4,5

1. Section of Cardiology, University of Illinois at Chicago, Chicago, IL, USA

2. Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, IL, USA 3.

Cardiovascular Research Center, Lifespan Rhode Island Hospital, RI, USA

4. The Warren Alpert Medical School, Brown University, RI, USA

5. Providence Veterans Affairs Medical Center, RI, USA

6. Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL,

USA

Background: Diabetes is associated with mitochondrial oxidative stress. We have shown that

myocardial oxidative stress leads to diastolic dysfunction in the hypertensive mouse model.

Therefore, we hypothesized that diabetes could cause diastolic dysfunction through mitochondrial

oxidative stress and that mitochondria-targeted antioxidant (MitoTEMPO) could prevent diastolic

dysfunction in a diabetic mouse model.

Methods and Results: C57BL/6J mice were fed either 60 kcal% fat diet (HFD) or normal chow

(control) for eight weeks with or without concurrent MitoTEMPO administration, followed by in

vivo assessment of diastolic function and ex vivo studies. HFD mice developed impaired glucose

tolerance compared with the control (serum glucose = 495 ± 45 mg/dL vs. 236 ± 30 mg/dL at 60

min after intraperitoneal glucose injection, p<0.05). Myocardial tagged cardiac magnetic

resonance imaging (CMR) showed significantly reduced diastolic circumferential strain (Ecc) rate

in the HFD mice compared with controls (5.0 ± 0.3 1/s vs. 7.4 ± 0.5 1/s, p<0.05), indicating

diastolic dysfunction in the HFD mice. Systolic function was comparable in both groups (LVEF=

66.4 ± 1.4% vs. 66.7 ± 1.2%, p>0.05). MitoTEMPO-treated HFD mice showed significant

reduction in mitochondria reactive oxygen species, S-glutathionylation of cardiac myosin binding

protein C (cMyBP-C), and diastolic dysfunction, comparable to the control. The fasting insulin

levels of MitoTEMPO-treated HFD mice were also comparable to the controls (p>0.05).

Conclusions: MitoTEMPO treatment prevented insulin resistance and diastolic dysfunction,

suggesting mitochondrial oxidative stress may be involved in the pathophysiology of both

conditions.

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162

PRO-INFLAMMATORY AND ANTI-INFLAMMATORY MAST CELLS IN OBESITY

AND DIABETES

Y. Zhou, G-P. Shi

Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston,

MA, USA

Mast cells contribute to the pathogenesis of obesity and diabetes. Deficiency or pharmacological

inactivation of mast cells protects mice from these metabolic diseases. This study demonstrates

that leptin deficiency slants otherwise pro-inflammatory mast cells toward anti-inflammatory

functions. Mast cells in the white adipose tissues of lean humans and mice are leptin-deficient.

Adoptive transfer of leptin-deficient mast cells expanded ex vivo mitigates diet-induced and pre-

established obesity and diabetes in diet-induced and genetic obese mice. Mechanistic studies show

that leptin-deficient mast cells polarize macrophages from M1 to M2 functions because of an

altered balance between pro- and anti-inflammatory cytokines, but do not affect T-cell

differentiation. Rampant body weight gain in ob/ob mice, a strain that lacks leptin, associates with

reduced mast cell content in the white adipose tissues. In ob/ob mice, genetic depletion of mast

cells exacerbates obesity and diabetes, and repopulation of bone marrow in vitro differentiated

mast cells ameliorates obesity and diabetes.

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163

ROLE OF REACTIVE OXYGEN SPECIES IN THE ADDED SUGAR-INDUCED

CARDIOVASCULAR DISEASE

K. Prasad

University of Saskatchewan, Saskatoon, SK, Canada

Consumption of high amount of sugars has been implicated in the pathophysiology of

cardiovascular diseases.

The objectives of this presentation are to determine if sugars generate reactive oxygen species

(ROS) and if cardiovascular diseases are associated with enhanced production of ROS. Various

mechanisms are involved in sugar-induced generation of ROS. Glucose metabolism increases the

formation of reduced nicotinamide -adenine –dinucleotide, and flavin adenine dinucleotide which

would increase the generation of superoxide anion in the mitochondria. High glucose

concentrations activate nicotinamide adenine dinucleotide phosphate-oxidase, and increase the

production of advanced glycation end products, insulin and uric acid which would increase the

generation of ROS. High consumption of sugars is reported to be associated with the development

of atherosclerosis, hypertension, coronary artery disease, cardiac arrhythmias, cardiomyopathy,

and peripheral vascular diseases. ROS also have been implicated in the pathophysiology of all of

the above mention diseases. In conclusion the data suggest that added sugar-induced

cardiovascular diseases are mediated through sugar- induced generation of ROS.

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164

EXERCISE IMPROVES VASCULAR INSULIN SENSITIVITY: ROLE OF

MITOCHONDRIAL ROS Y. Mao, Z.X. Hou, X. Zhang, Y. Zhang, F. Gao

School of Aerospace Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China

Vascular insulin resistance contributes to elevated peripheral vascular dysfunction and subsequent

hypertension. Excessive production of oxidants, decreased NO bioavailability, and decreased local

antioxidant capacity in the vasculature are central causes of vascular insulin resistance. We found

that reactive oxygen species (ROS) production was increased in the mesenteric arterioles of

spontaneously hypertensive rats (SHRs). Among many sources of increased vascular ROS

production in hypertension, mitochondrial ROS overproduction plays an important role. Treatment

with the mitochondria-targeted antioxidant decreased mitochondrial superoxide level which has

therapeutic benefits in endothelial insulin resistance-related vascular dysfunction and

hypertension. Exercise training that can improve vascular insulin sensitivity may have significant

value in prevention and treatment of hypertension. Our findings suggest that exercise training

beginning at the early hypertensive stage in young SHRs ameliorates hypertension via improving

vascular insulin sensitivity. However, the beneficial effects of exercise training on vascular

function have not been fully elucidated. Recent evidence has suggested that chronic aerobic

exercise training in old rats preserved aortic mitochondrial function as evidenced by reduced ROS

formation, increased ATP formation and restored activities of electron-coupling capacity. Regular

exercise training reduces vascular expression of NAD(P)H oxidase resulting in decreased local

ROS generation. Our study also indicates that exercise ameliorates myocardial insulin resistance

by rescuing mitochondrial response to insulin via an eNOS-dependent manner. Furthermore,

targeting mitochondria to restore mitochondria-ROS homeostasis is a promising intervention to

reduce vascular insulin resistance. Taken together, our results demonstrate that exercise improves

cardiovascular insulin sensitivity and vascular function through enhancing mitochondrial function

and restoring mitochondria-ROS homeostasis.

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165

ASLEEP, BUT NOT DAYTIME CLINIC OR AWAKE MEAN, BLOOD PRESSURE IS

AN INDEPENDENT PREDICTOR OF CARDIOVASCULAR EVENTS IN PATIENTS

WITH DIABETES: THE HYGIA PROJECT R.C. Hermida1, A. Moya2, J.J. Crespo3, A. Otero4, M. Dominguez-Sardina3, M.T. Rios3,

M.C. Castineira5, A. Mojon1, J.R. Fernandez1, D.E. Ayala1





5. Servicio Gallego de Salud, Lugo, Spain

Objectives: Recent guidelines suggest relying on the ambulatory blood pressure (BP) monitoring

(ABPM) derived awake mean to corroborate the diagnosis of hypertension suspected by elevated

clinic BP measurement. However, several prospective ABPM studies have found elevated sleep-

time BP is a better predictor of cardiovascular (CVD) risk than awake BP mean, also in diabetes.

We evaluated the combined contribution to CVD risk of clinic, awake, and asleep BP among

patients with diabetes participants in the Hygia Project, designed to evaluate prospectively CVD

risk by ABPM.

Methods: This study involved 2632 patients with type 2 diabetes, 1589 men/1043 women,

65.1±11.6 years of age, prospectively evaluated throughout a 4.1-year median follow-up. BP was

measured at 20-min intervals from 07:00 to 23:00h and at 30-min intervals at night for 48h.

Results: The hazard ratios (HR) of total CVD events for each 1-SD elevation in clinic, awake, and

asleep systolic BP (SBP) analyzed separately (adjusted for the significant influential characteristics

of age, sex, chronic kidney disease, cigarette smoking, waist perimeter, and history of previous

CVD event) were 1.25 [95%CI: 1.17-1.35]; 1.39 [1.30-1.50], and 1.51 [1.41-1.62], respectively

(always P<0.001). Exploration of the combined contribution of all three BP measurements

revealed elevation in asleep SBP (HR=1.55 [1.38-1.75], P<0.001) but not in clinic BP (1.08 [0.99-

1.18], P=0.082) or awake BP (0.93 [0.82-1.06], P=0.270) was the only independent BP parameter

significantly associated with increased CVD risk.

Conclusions: In patients with diabetes, sleep-time SBP mean, but not daytime clinic BP

measurement or ABPM-derived awake BP mean, is the only significant and independent

prognostic marker of CVD morbidity and mortality. These findings indicate ABPM, but not

conventional clinic BP so far mistakenly used to diagnose hypertension and establish therapeutic

targets, is a clinical necessity to accurately detect abnormal sleep-time BP and assess CVD risk in

diabetes.

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166

RISK OF DIABETES INCIDENCE WITH STATIN TREATMENT: STUDY USING

NATIONWIDE DATABASE FOR HEALTHCARE RESEARCH T.A. Ahmad1, C. Chuang1, D. Leslie1, G. Liu1, P. Alagona1, A. Foy1, S.M. Bokhari2

1. Penn State Hershey Medical Center, Hershey, PA, USA

2. Kuwaiti Hospital, Sharjah, United Arab Emirates

Introduction: Statins are one of the few drugs that have a dramatic effect on health outcome. Some

recently published studies have shown increased trends towards incidence of diabetes (DM) in

statin-users. We used MarketScan® database that captures claims data from a selection of large

employers and health plans, including commercial insurance companies with information on over

85 million covered lives.

Method: A matched case control study sample is selected with predefined inclusion & exclusion

criterion using the ICD-9 codes during first year of enrollment period. Then cases were selected

based on statin exposure (index date) and matched with controls (unexposed) based on their age,

gender and geographic location. They were then followed from the index date till the end of study

for a minimum of two years for DM incidence. Data on hypertension, coronary artery disease,

peripheral vascular disease, stroke, and hyperlipidemia is collected as dependent variables. Cox

proportional hazard model is used to perform the analyses.

Results: Study population includes 231,478 matched pairs of cases & controls with mean age of

51.3(±7.5) years. Statins have shown an increase in DM incidence (adjusted HR 2.33, 95%CI 2.28,

2.39). A linearly increasing trend in hazard ratio has been noticed with every 10 years age increase.

Compared to males, females are more likely (adjusted HR 1.08; 95% CI 1.06, 1.10) to develop

DM while on statins.

Conclusion: Statins raise the risk of diabetes development that increases with age. Females, with

generally smaller body sizes, have higher risk of DM incidence compared to males.

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167

FEMORAL AND AORTIC INTIMA-MEDIA THICKNESS BUT NOT CAROTID OR

BRACHIAL INTIMA-MEDIA THICKNESS ARE ABNORMAL IN CHILDREN WITH

TYPE 1 DIABETES C. Lilje1, J.P. Cardinale1, J. Cronan1, L. Kashyap1, P. Clesi2, E. Oral2, R. Gomez1,

J. Hempe1,2, S. Chalew1

1. Louisiana State University Health Sciences Center, New Orleans, LA, USA

2. Research Institute, Children's Hospital, New Orleans, LA, USA

Objective: To investigate feasibility and sensitivity of Intima-Media Thickness (IMT) analysis at

the level of the brachial artery, femoral artery and abdominal aorta compared to the carotid artery

in children with type 1 diabetes mellitus (T1DM).

Background: T1DM patients are at risk for cardiovascular disease. IMT – commonly measured as

carotid IMT – is an established marker for early cardiovascular risk in adults but rarely used in

children. However, autopsy studies have shown atherosclerotic changes even in early childhood

and most prominently in the abdominal aorta.

Methods: Using high-resolution external ultrasound, IMT was analyzed as carotid, brachial,

femoral, and aortic IMT in established pediatric T1DM patients (group I) and healthy controls

(group II). Excluded were individuals with other cardiovascular risk factors (smoking, obesity,

dyslipidemia, hypertension).

Results: 63 subjects were studied (group I=25; group II=38). Groups were matched regarding age

(13.6±3.6 vs. 13.2±4.3y, p=ns), sex, and BMI. Carotid, brachial, femoral and aortic IMT analyses

were feasible in 100%, 83%, 91% and 94% of subjects, respectively. Reproducibility was

excellent. IMT was increased in T1DM patients if analyzed at the level of the femoral artery

(0.40±0.06 vs. 0.36±0.06mm, p=0.002) or aorta (0.58±0.11 vs. 0.52±0.10mm, p=0.011). IMT was

not different between groups if analyzed at the level of the carotid or brachial artery.

Conclusion: IMT analysis at the level of the femoral artery and aorta was feasible in the vast

majority of children. Femoral and aortic IMT analyses detected early vascular changes in teenage

T1DM patients while carotid and brachial IMT analyses did not.

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168

THE EFFECTS OF A LIFESTYLE INTERVENTION PROGRAM ON CENTRAL

OBESITY OF PEOPLE WITH METABOLIC SYNDROME S.W.S. Lo, S.Y. Chair, F.K. Lee

The Nethersole School of Nursing, The Chinese University of Hong Kong, HKSAR

Purpose of the study: The purpose of this study is to examine the effects of a lifestyle intervention

program (LIPMS), on central obesity and other health outcomes of people with metabolic

syndrome (MS), guided by the extended Health Belief Model (eHBM).

Methods: This cluster-randomized controlled trial invited participants with two or more MS

components by the American Heart Association definition. Participants in the intervention group

received a 3-month LIPMS program while participants in the control group received an attention

placebo. The mixed effects model was adopted to evaluate outcomes included body weight, waist

circumference, blood pressure, fasting glucose, and fasting lipid profiles. These measures were

further evaluated to indicate the presence of MS.

Results: The final sample consisted of 183 adults (19.1% male) with the mean age of 54.0 years

(SD 7.8). More than one-third had one or more chronic diseases and half had MS. At 3 months,

the outcomes of both groups exhibited a favorable trend from baseline to the end of intervention.

Overall MS prevalence reduced for 13.8%. After controlling for age, gender, education level and

total number of chronic diseases, statistical differences were found in the change of total

cholesterol (standardized coefficients=0.065, p=0.035) and waist circumference (standardized

coefficients=0.146, p=0.008) between the intervention and control group after participation in

LIPMS.

Conclusions: A lifestyle intervention program based on the eHBM was effective in improving

health of people with MS. The current findings provide empirical information under a theoretical

framework for improving health services targeting MS.

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RISK STRATIFICATION AND SECONDARY PREVENTION OF CVD

169

EFFECTIVELY SCREENING FOR CORONARY ARTERY DISEASE IN PATIENTS

UNDERGOING ORTHOTOPIC LIVER TRANSPLANT EVALUATION

B. Lee, F. Li, J. Hanje, S. Lilly

The Ohio State University, Columbus, OH, USA

Coronary artery disease (CAD) is prevalent in patients with end-stage liver disease and associated

with poor outcomes among those undergoing orthotopic liver transplant (OLT). Non-invasive

screening for CAD in this population is less sensitive than in the general population. We describe

our institutional experience among patients undergoing CAD screening in the course of OLT

evaluation.

Methods: We retrospectively identified all patients that underwent CAD screening in the course

of OLT evaluation between May 2009 and February 2014. Demographic, clinical and procedural

characteristics were collated and analyzed.

Results: Within the patient cohort (n = 135), the mean age was 56 (range 32 – 71), and 92 (70%)

were male. Among those undergoing angiography, obstructive CAD was common (n = 38;

28%). The number of traditional risk factors was linearly associated with CAD, and those with

two or more risk factors were found to have CAD by angiography 50% of the time (OR 1.92; CI

1.07 – 3.44, p=0.026, Fig. 1).

Conclusion: Obstructive CAD is common among patients with advanced liver disease. Our data

supports coronary angiography in pre-OLT patients with two or more risk factors. Whether or not

this affects outcomes awaits ongoing prospective reports.

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170

NON-INVASIVE RISK STRATIFICATION WITH STRESS SINGLE PHOTON

EMISSION COMPUTED TOMOGRAPHY IN PATIENTS WITH MYOCARDIAL

INJURY FOLLOWING NON-CARDIAC SURGERY

E. Bangert

McMaster University, Hamilton, ON, Canada

Myocardial injury following non-cardiac surgery (MINS), as measured by postoperative troponin

elevation, is the most common major vascular complication after non-cardiac surgery. Myocardial

infarction (MI) is the most common vascular complication following major surgery, and many

patients with evidence of MINS will have had a perioperative MI. Risk stratification and the

selective revascularization has been shown to reduce cardiovascular events in the non-

perioperative MI setting, however, its utility in the perioperative setting is not established, and

only a minority with MINS undergo such a strategy.

Methods: This study has consisted of a retrospective chart review of 567 patients conducted at

McMaster University. We have screened patients between 2009-2014 who underwent a SPECT

myocardial perfusion study within 2 months following hospital admission for surgery. Patients

were included in this analysis if 1) there was evidence of MINS, defined as an abnormal troponin

value in the post-operative period during the index admission, and 2) the nuclear study was

performed for the purpose of risk stratification for the postoperative event. Our primary objective

determined the association between the degree of ischemia identified on SPECT and the composite

outcome of death, MI at 6 months. Secondary analyses evaluated the feasibility of the test in this

patient population.

Results: Of the patients analyzed 120 patients were with MINS. The patients who experienced

MINS were older, more likely to have diabetes, and have hypertension. The 6-month mortality

rate was 2.3% (93% CI, 1.5%-1.9%). SPECT predict major cardiovascular events in individuals

with MINS (92% CI, 1.27-2.23).

Conclusion: SPECT is a promising tool for providing better care for patients with MINS. The

study has shown that the use of SPECT permitted early detection of major cardiovascular events

in individuals with MINS. The peak troponin values were associated with higher 6-month

mortality myocardial infarction as well as revascularization.

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171

DO WE KEEP CARDIAC PATIENTS OUT OF HOSPITAL BY ADDING

TELEREHABILITATION TO STANDARD REHABILITATION? I. Frederix1,2,4, D. Hansen1, N. Van Driessche2, K. Coninx1, P. Vandervoort3,

C. Vrints4, E. Van Craenenbroeck4, P. Dendale1,2

1. Department of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium

2. Department of Cardiology, Jessa Hospital, Hasselt, Belgium

3. Department of Cardiology, Ziekenhuis Oost-Limburg (ZOL), Genk, Belgium

4. Department of Cardiology, Antwerp University Hospital, Antwerp, Belgium

Background: Standard in-hospital cardiac rehabilitation (CR) has been proven to be effective.

Cardiac patients however often do not attend these rehabilitation sessions leading to non-

compliance with lifestyle and risk factor recommendations, which is associated with increased

adverse outcomes.

Objectives: We investigated whether the addition of an internet-based rehabilitation program to

standard CR can reduce the number of cardiovascular rehospitalisations.

Methods: The Telerehab III study is a multi-centric randomized controlled trial, that runs from

February 2013-2015. Coronary artery disease or heart failure patients were eligible. Intervention

patients (n=70) were, at study start, stratified in different subgroups based on their cardiovascular

risk factor profile and cardiopulmonary exercise testing. This stratification enabled the caregiver

to provide each patient with a personalised diet and exercise protocol. The intervention patients

were asked to wear a motion sensor continuously for a total study period of 6 months. Each week,

they received feedback messages (via e-mail and/or SMS) to gradually increase their activity level

and to inform them about healthy diets. Control patients (n=70) wore taped motion sensor three

times for 9 days (week 1, 6 and 24) for measurement purposes only. They did not receive feedback

regarding their physical activities via SMS or e-mail, nor did they receive dietary advice.

Results: The Kaplan-Meier curve showed a significant lower rehospitalisation rate in the

intervention group (P=0.01055) (13 rehospitalisations), when compared to the control group (29

rehospitalisations).

Conclusions: The addition of an internet-based telerehabilitation program to standard CR can

impact favorably on cardiovascular rehospitalisation rate.

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172

HEART ATTACK ANXIETY: THE IRONY BEHIND PHYSICAL ACTIVITY

RECOMMENDATIONS FOR POST-MI PATIENTS K.W. Davidson, J.A. Shaffer, K.M. Diaz, N. Moise, I. Kronish, S. Ye, C. Alcantara

Columbia University, New York, NY, USA

Background: The American Heart Association (AHA) recommends 30 minutes of moderate-to-

vigorous exercise five or more times a week for most patients surviving a myocardial infarction

(MI). The characteristics of those who will maintain this lifestyle recommendation are currently

unknown.

Methods: We conducted a nationally representative survey of 1500 U.S. adults previously

diagnosed with an MI. Patients reported their demographics, usual physical activity pattern, and

nominated their single most important current health concern. Patients were categorized into those

who did and did not meet the AHA exercise recommendation, using the validated, single-item

question assessing days per week of moderate or vigorous physical activity >30 minutes.

Results: 38% of respondents were female and the average age was 60.9 years (+ 11.9 SD). 18%

of patients reported that “worsening of heart problems” was their single most important health

concern. 24% reported regular exercise at the level recommended by the AHA. Ironically, those

who reported worsening heart problems as their single most important health concern were

significantly more likely to not meet the exercise recommendation in multivariable analysis,

(adjusted odds ratio [aOR] 1.40, 95% CI 1.01-1.94), as were women (aOR 1.40, 95% CI 1.09-

1.81) and those over 65 years of age (aOR 1.34, 95% CI 1.03-1.75).

Discussion: For patients surviving a MI, adherence to exercise guidelines was worse among those

who were most concerned about a decline in their heart health. Appropriately tailoring an exercise

message to those surviving, and worrying about heart disease, may require interventions derived

from fear and avoidance science.

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173

OPIUM ADDICTION AND EARLY AND 6-MONTH OUTCOMES OF PATIENTS

WITH ST ELEVATION MYOCARDIAL INFARCTION M. Mousavi1, S. Kalhor2, J. Tahmasebi3, M. Alizadeh1

1. Alborz University of Medical Sciences. Karaj, Iran

2. Islamic Azad University, Shahroud, Iran

3. Shahroud University of Medical Sciences, Shahroud, Iran

Background: Myocardial infarction is one of the most important causes of mortality worldwide.

To date multiple risk factors have been described but still the role of opium addiction is not

clarified yet and there are many unproved believes about it.

Objectives: This study is performed to evaluate if opium addiction has any effect on early and 6

month outcomes of ST elevation myocardial infarction (STEMI).

Methods: This cohort study was performed on 334 patients with STEMI in Shahroud, Iran, during

years 2009-2012. There were 117 patients with opium addiction and 217controls. Patients were

followed up during hospitalization and for 6 months and the primary endpoint of the study was a

composite of death, heart failure, recurrent chest pain and recurrent STEMI.

Results: The primary end point of the study was not significantly different neither during in-

hospital nor 6–month follow up (P>0.05). Some risk factors of coronary artery disease (CAD),

including hypertension, diabetes and hyperlipidemia were seen less in opium addiction group

(P<0.05), but family history of CAD was not significantly different.

Conclusion: The present study showed that although opium addicted patients had less risk factors

of CAD, in-hospital and 6-month adverse outcomes were not significantly different in STEMI

patients with or without opium addiction.

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174

CORONARY ARTERY DISEASE AND SERUM APELIN LEVELS: A META-

ANALYSIS P. Agasthi1, A. Chenna1, R. Vankina2, S. Aloor2, R. Harris1


2. Miller School of Medicine, University of Miami, Miami, Florida, USA

3. Baystate Medical Center, Springfield, Massachusetts, USA

Background: Apelin is peptide produced by adipose tissue that appears to function as an

endogenous ligand for the orphaned G-protein-coupled receptor (APJ). The Apelin/APJ system

plays a role in regulating cardiovascular system physiology and homeostasis. It is suggested that

apelin/APJ system may possess an anti- atherogenic effect via endothelium-dependent

vasodilation and down regulating expression of adhesion molecules and chemokines leading to

reduced vascular inflammation. The association between serum apelin and coronary artery disease

(CAD) is obscure.


between circulating apelin levels and CAD.


serum apelin levels in the CAD and non CAD study population. We included case controls, cohort

and cross-sectional studies. We calculated the weighted standardized mean difference (SMD) in

serum apelin levels between the CAD and control groups.


participants. The median age of the CAD group was 58.9yrs (IQR 55.7 – 63.4) compared to 56.1yrs

(IQR 43-56.1) in the control group. The median body mass index in the CAD group was 24.9

kg/m2 (IQR 24.9-25.1) compared to 24.2 kg/m2 (IQR 23.7-24.7) in the control group. The

unweighted median serum apelin levels in the CAD group were 0.54 ng/ml (IQR 0.05-0.66)

compared to 1.98 ng/ml (IQR 0.07-3.11) in the control group. The SMD of serum apelin level was

-2.53 (95% CI -3.50, -1.56) p<0.001 comparing those in the CAD and control group.

Conclusion: Serum apelin levels are significantly and negatively associated with CAD. Further

studies are needed to clarify the role of apelin in the development of CAD and its potential to serve

as a novel biomarker.

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175

ST DEPRESSION IN LEAD AVL AS A POTENTIAL PREDICTOR OF POOR

OUTCOME AND PROGNOSIS FOR NSTEMI PATIENTS N. Parikh1, K. Sivakumar2, R. Nunes1, I. Laptevsky1, C. Agarwal1, G. Singh1,

B. Simmons1, G. Fernaine1, G. Hassen1

1. NYU Lutheran Medical Center, Brooklyn, NY, USA

2. St. George's University, True Blue, Grenada, West Indies

Introduction: ST depression in lead aVL has been postulated to predict poor outcome after acute

myocardial infarction (AMI). The objective of this study is to investigate the correlation between

ST depression in lead aVL and multi-vessel coronary disease in patients with Non-ST elevation

MI (NSTEMI) and the outcome of these patients.

Methods: Charts of all patients that underwent diagnostic coronary angiography for NSTEMI at

an urban community hospital were retrospectively reviewed. The ECGs of all patients were

reviewed for changes in lead aVL. ECGs were recorded in 12-lead format and reviewed by two

independent physicians (one cardiologist and one emergency department physician). ST-segment

depressions in lead aVL were noted. Coronary angiogram results were studied and the correlation

between the ST segment depression and the number of vessels affected examined. In addition, in-

hospital mortality, length of hospital and intensive care unit stay, readmission rate as well as the

need for coronary artery bypass graft (CABG) was studied.

Results: 218 patients underwent percutaneous coronary intervention (PCI) for NSTEMI. 42

patients (19.3%) were found to have ST segment depression in lead. Of these 42 patients who had

STD in lead aVL, 12 patients (29%) had triple vessel disease (TVD) and 3 patients (7.1%) had left

main disease (LMD). Seven patients (16.7%) underwent coronary artery bypass graft (CABG) of

which two patients (28.6%) had LMD. All seven of the patients (100%) had TVD. Five patients

(71.4%) were male and two patients (28.6%) were female. The average age for these patient groups

was 75 years.

Conclusion: ST depression in lead aVL was increasingly associated with TVD and LMD and may

predict significant coronary artery disease. This study can help identify patients with NSTEMI that

require aggressive management and early coronary catheterization. Further studies with patients

who have NSTEMI are required to verify these findings.

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176

DYNAMIC LEFT VENTRICULAR OUTFLOW TRACT OBSTRUCTION:

ECHOCARDIOGRAPHY GUIDED CLINICAL RISK PREDICTION IN CRITICAL

CARE SETTINGS M.K. Mittal1, Y. Pak2, K.C. Dellsperger3, A. Anand Chockalingam1

1. University of Missouri, Columbia, MO, USA

2. Department of Biostatistics, UCLA Clinical and Translational Science Institute, Torrance, CA,

USA

3. Georgia Regents Health System, Augusta, GA, USA

Introduction: Dynamic left ventricular outflow tract obstruction (LVOTO) is increasingly

recognized in critically ill patients. The aim of this study is to identify clinical risk predictors that

may identify high risk patients as predicted by echocardiographic features. Methods: Clinical and

demographic data of all patients diagnosed with acute LVOTO were matched with a randomly

derived control group to develop a clinical scoring model. Subsequently, consecutive patients

(n=167) admitted to intensive care units (July 2007 - November 2009) and underwent

echocardiography were screened to identify 143 patients. Using pre-determined echocardiographic

criteria, a blinded observer classified all patients as either high or low risk for developing LVOTO.

Results: The cross sectional study could not validate the clinical score because it did not

differentiate between different LVOTO risk groups (p=0.54). Univariate analysis suggested female

sex (high vs low risk, 64% vs 32%; p=0.009), advanced age (74.8 ± 14.1 vs 57.8 ± 18.4; p=0.0004)

and lack of inotrope use (35% vs 61%; p=0.03) to be significantly associated with high risk

LVOTO group. All other variables were insignificant. Based on the multiple logistic regression,

age (p= 0.003) was found to be the only independent predictor of high risk for developing LVOTO,

with the estimated area under the ROC curve (AUC) being 0.81.

Conclusion: Elderly patients are at high risk of developing dynamic LVOTO. Other clinical and

demographic parameters did not reliably predict risk in our study. Larger studies are warranted to

validate clinical risk prediction models to better manage this potentially life threatening cardiac

condition.

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VALVULAR / CONGENITAL HEART DISEASE, CARDIAC SURGERY

177

POSTINFARCTION VENTRICULAR DEFECT: OPERATE OR WAIT? L.P. Perrault1,2, A. Nguyen1,2, Q. De Hemptinne1,2, P-E Noly1, R. Ibrahim1,2,

D. Bouchard1,2, M. Carrier1,2, R. Cartier1,2, P. Demers1,2, M. Pellerin1,2

1. Montreal Heart Institute, Montreal, QC, Canada

2. University of Montreal, Montreal, QC, Canada

Objectives: The objective of this paper was to study the clinical application of our decision

algorithm in the treatment of post-infarction VSD at the Montreal Heart Institute.

Methods: Between April 2004 and August 2014, 35 consecutive patients with post-infarction VSD

were treated. Twenty-three patients underwent surgery, and twelve patients were treated with

percutaneous closure of VSD during the same period.

Results: The mean age was 67.9 ± 10.1 years and 70% of patients were male. Before surgery, 78%

of patients were in cardiogenic shock and 87% were supported had IABP pump. The preoperative

EuroSCORE II was 21.9 ± 14.5%.. 74% of patients were in New York Heart Association

functional class III or IV preoperatively. The mean time between acute myocardial infarction and

the VSD diagnosis was 6.7 ± 4.1 days and between VSD diagnosis and surgery was 1 day. The

average VSD size was 19.4 ± 9.7 mm and 74% were located in apical position. 2 patients had

failed Amplatzer before surgery. 65% of patients underwent concomitant coronary bypass surgery

with an average of 1 ± 1.1 grafts, and 26% patients underwent other concomitant procedures. 52%

of patients developed acute renal failure with 35% requiring temporary dialysis. Mild to moderate

residual VSD was present in 35% of cases and dehiscence of the patch was found in 13% of cases,

requiring reoperation. The overall mortality was 22% at 30 days. In the percutaneous occlusion

treatment group (n = 12), the 30-day mortality was 58% and mild to moderate residual VSD

persisted in 42% of cases.

Conclusion: The early management of stable VSD is associated with acceptable mortality rates.

The emergence of new technologies (ventricular assistance device, percutaneous Amplatzer) could

stabilize critical patients, but their role is not yet well defined.

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178

THE ROLE OF PHARMACOLOGICAL THERAPY IN CHRONIC HEART VALVE

DISEASES

J.S. Borer

SUNY Downstate Medical Center, Brooklyn and New York, NY, USA

Valvular heart diseases (VHDs) are progressive. When they are “primary”, i.e., due to intrinsic

abnormality of valve structure and not secondary to comorbid conditions (e.g., ischemia), they

generally are characterized by long asymptomatic phases during which cardiac functional and

hemodynamic debility progresses. Ultimately, these developments lead to symptoms, other

morbidities and, finally, death. Treatment depends on VHD type and severity. However, when

VHDs are hemodynamically/functionally severe and symptomatic, therapy generally requires

mechanical intervention (replacement or repair). Asymptomatic patients, and those who lack

objective descriptors that predict high imminent risk, are managed by close clinical observation

and efforts to minimize associated cardiovascular risk factors until surgical indications develop.

In this setting, drugs often are prescribed based on theoretical concerns or preclinical studies or

small clinical studies involving “surrogate” rather than clinical endpoints. However, no rigorous

evidence supports pharmacological therapy in most chronic situations. For Aortic Stenosis,

multiple drugs (statins, ACE inhibitors, bisphosphonates, etc.) have been tested. Rigorous

randomized controlled trials are available only with statins and these generally have shown no

benefit. For Aortic Regurgitation, multiple direct and indirect vasodilators have been studied,

generally for effect on surrogate, rather than clinical, outcomes; the only drug shown in

randomized controlled trials to benefit outcome has been long-acting nifedipine, and that benefit

seems to have been largely related to effect on the comorbidity of hypertension. For Mitral

Stenosis, no drugs have been rigorously studied for clinical outcome. For Mitral Regurgitation,

few studies are available and all have been neutral or negative (i.e., potentially harmful). Based on

these findings, hemodynamically active drugs generally should be avoided in asymptomatic

patients with primary valve disease.

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179

FIRST-IN-HUMAN TRANSCATHETER MITRAL VALVE REPLACEMENT FOR

NATIVE MITRAL VALVE REGURGITATION

J. Ye

St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada

Mitral regurgitation is a common valvular heart disease. The prevalence increases with age.

Therefore, with the aging of the population, a continuing increase in the prevalence of mitral

regurgitation is expected in the coming years. Surgical mitral valve repair or replacement is the

standard treatment of mitral regurgitation. However, a study has demonstrated that 49% of patients

with severe mitral regurgitation were declined for mitral valve surgery due to impaired left

ventricular systolic function, older age, and significant comorbidity. Moreover, the benefit of

surgical treatment of functional or ischemic mitral regurgitation remains controversial. As

transcatheter aortic valve implantation, developing transcatheter mitral valve replacement would

benefit the patients with severe mitral regurgitation who are declined valve surgery. In recent

years transcatheter mitral valve replacement has aroused significant interest and many

transcatheter valve devices have been developed. However, there were only a few first-in-human

(FIH) transcatheter mitral valve replacement cases that were performed worldwide. We performed

our first transapical transcatheter mitral valve replacement with the Edwards FORTIS self-

expandable transcatheter mitral valve in an 81 years old patient with symptomatic severe

functional mitral regurgitation and left ventricular dysfunction, who was not a surgical candidate

for open-heart surgery. The FORTIS valve was successfully implanted under the guidance of

echocardiography and fluoroscopy. No contrast or rapid ventricular pacing was required. At 6-

month follow-up, the patient heart failure symptom was improved significantly. The follow-up

echocardiography showed normal function of the well-seated FORTIS valve with trivial

paravalvular leak and no mitral regurgitation, as well as positive LV remodeling with improved

left ventricular systolic function. Transcatheter mitral valve replacement is challenging, but shows

tremendous promise.

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180

AORTIC VALVE DISEASE MANAGEMENT FOR THE 21ST CENTURY: THE

UNFOLDING OF TAVR REVOLUTION

A.N. Cheema

University of Toronto, Canada

Transcatheter aortic valve replacement (TAVR) has become the preferred therapy for the treatment

of aortic stenosis compared to surgical aortic valve replacement among high-risk patients. The

enthusiasm from the success of TAVR in high risk patients is affecting management decisions for

all patients with aortic valve disease and application of TAVR is being used for patients not

included in the landmark studies done for regulatory approval.

In addition to inoperable or high surgical risk patients with native aortic stenosis, TAVR has

demonstrated promising medium term results for treatment of failed aortic and mitral

bioprosthesis. At present, clinical trials are also underway to examine the role of TAVR as the

initial management strategy compared to surgical aortic valve replacement for low to moderate

surgical risk patients. With the advent of new technology and evolution of existing devices, an

even greater number of patients with aortic valve disease may benefit from TAVR therapy.

This presentation will review the epidemiology of aortic stenosis; describe recent trends in the

surgical management of aortic valve disease and discuss implications for TAVR therapy in the

next decade. Furthermore, the promise offered by the 2nd generation transcatheter heart valves,

recent data for long term durability and TAVR trends across countries will be presented.

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181

LIPID LOWERING IN PATIENTS WITH MILD AORTIC STENOSIS AND ELEVATED

LOW DENSITY LIPOPROTEIN: THE SEAS STUDY A.M. Greve1, C.N. Bang1, C. Gohlke-Baerwolf2, K. Boman3, K. Egstrup4,

Y.A. Kesäniemi5, S. Ray6, T.R. Pedersen7, N.M. Rajamannan8,9, K. Wachtell1,10 1. Department of Cardiology, Glostrup University Hospital, Copenhagen, Denmark

2. Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany

3. Department of Medicine, Institution of Public Health and Clinical Medicine, Umeå University,

Skelleftå, Sweden

4. Medicinsk Afdeling, OUH Svendborg Sygehus, Denmark

5. Institute of Clinical Medicine, Department of Medicine, University of Oulu and Clinical Research

center, Oulu University Hospital, Oulu, Finland

6. University Hospitals of South Manchester, Manchester Academic Health Sciences Centre, Manchester,

United Kingdom

7. Center for Preventive medicine, Oslo University Hospital, Ullevål and University of Oslo, Oslo,

Norway

8. Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester MN; USA

9. Most Sacred Heart of Jesus Cardiology and Valvular Institute, Sheboygan, WI, USA

10. Department of Cardiology, Örebro University Hospital, Örebro, Sweden

Aims: To examine if pretreatment low density lipoprotein cholesterol (LDL) levels and aortic

stenosis (AS) severity alter the efficacy of lipid-lowering therapy in AS patients.

Methods and Results: Asymptomatic patients with AS randomized (1:1) to 40 mg Simvastatin +

10 mg Ezetimibe combination vs. placebo and ≥2 echocardiograms in the SEAS trial. The main

endpoint in this substudy was impact of randomization on the association between pretreatment

LDL levels and progression in AS severity, as determined by peak aortic jet velocity and a

composite cardiovascular endpoint. Treatment effect was analyzed by separating patients into

quartiles of LDL levels in mild and moderate-to-severe AS (>3.0 m/sec). A total of 1,682 patients

were followed for a mean of 4.4 years (7,373 patient-years of follow-up). Among patients in the

highest quartile of LDL with mild AS at baseline (p=0.03 for interaction), Simvastatin-Ezetimibe

was associated with lesser end of study progression in peak jet velocity (OR 0.85, 95% CI: 0.74 –

0.98, p=0.03). In a parallel analysis, Simvastatin-Ezetimibe also reduced composite endpoints in

the highest quartile of LDL with mild AS at baseline (HR 0.46, 95% CI: 0.23 – 0.90, p=0.02).

Conversely, there was no detectable effect of Simvastatin-Ezetimibe combination on AS

progression in the other LDL quartiles with mild AS baseline (p=0.75). No effect of lipid lowering

was noted in patients with moderate to severe aortic stenosis irrespective of pretreatment LDL

levels (p=0.87).

Conclusion: In a non-prespecified post-hoc analysis, asymptomatic patients with mild AS and

elevated LDL benefited from lipid-lowering therapy (SEAS study: NCT00092677).

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182

MISCONCEPTIONS AND DIAGNOSTIC CHALLENGES IN BIOPROSTHETIC

VALVE THROMBOSIS

S.V. Pislaru

Mayo Clinic, Rochester, MN

Bioprosthetic valve thrombosis (BPVT) is a rare, but potentially life-threatening complication. In

a review of the Mayo Clinic experience we found that BPVT was systematically under-reported

on TTE, and that most cases occurred late post-implantation. Furthermore, oral anticoagulation

with vitamin K antagonists resulted in hemodynamic and clinical improvement with minimal risk,

and should be considered first line therapy in hemodynamically stable patients. Echocardiographic

criteria for improving BPVT diagnosis are proposed.

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183

MANAGEMENT OF ASYMPTOMATIC AORTIC STENOSIS: WHAT IS NEW IN 2015?

H.P. Chaliki

Mayo Clinic, Scottsdale, AZ, USA

Calcific aortic stenosis is now the primary etiology of aortic stenosis in the majority of patients.

Risk factors such as hyperlipidemia play an important role in the progression of aortic stenosis.

According to the most recent American College of Cardiology/American Heart Association

guidelines, peak velocity greater than 4 m/sec, or a mean gradient of more than 40 mmHg and a

valve area of less than 1.0 cm2 is considered hemodynamically severe aortic stenosis. Aortic valve

surgery promptly should be done in symptomatic patients due to dismal prognosis without

operation. Features such as reduced left ventricular ejection fraction (<50%), very high velocity

(>5 m/sec) or a high mean gradient (>60 mm Hg) or a positive exercise test identify high risk

asymptomatic patients who would benefit from early aortic valve surgery. Recently, it was

recognized that up to 25% of severe aortic stenosis patients may have low trans-valvular gradient

despite preserved left ventricular ejection fraction due to concentric remodeling and high vascular

resistance. Although challenging, identification of this subgroup is important due to reduced long

term survival without surgery. Currently percutaneous aortic valves are used only in very high-

risk patients with severe symptomatic aortic stenosis. Their role may expand in the future,

depending on the technological advances and operator experience.

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184

ROLE OF CILIA IN CONGENITAL HEART DISEASE

M. Zahid

Dept. of Developmental Biology, University of Pittsburgh, PA, USA

Motile cilia at the embryonic node and in the respiratory tract are required for left-right patterning

and for muco-ciliary clearance from the respiratory tract, respectively. The heart is one of the most

asymmetric organs in the body in order to support two separate circulatory systems, the pulmonic

and systemic circulations, in parallel. Hence defects in ciliary function could contribute to

abnormal heart development resulting in congenital heart disease (CHD) as well as increased

respiratory complications. This dual role is exemplified by patients with primary ciliary dyskinesia

(PCD) in which patients have abnormal respiratory ciliary function leading to severe respiratory

complications over time as well as ~50% of patients having complete reversal of visceral organ

situs or situs inversus totalis.

Laterality defects are characterized by randomization of left-right patterning in thoraco-abdominal

visceral situs. We have shown that patients with complex CHD with heterotaxy have a high

prevalence of ciliary motion (CM) abnormalities as demonstrated by abnormally low nasal nitric

oxide (nNO) levels as well as high-speed video-microscopy of ciliated nasal epithelial tissue.

These CHD patients with CM abnormalities had increased respiratory symptoms reminiscent of

PCD patients and were enriched for mutations in genes typically associated with PCD. We have

also extended this work with studies on patients with transposition of the great arteries (TGA),

both D- and L-TGA, and show that these patients, similar to heterotaxy patients, have a high

prevalence of abnormal CM, borderline or PCD level abnormal nNO levels, increased respiratory

symptoms as compared to TGA patients without CM abnormalities, and are enriched for novel or

rare coding variants in the genes typically associated with PCD. In addition we have shown that

a wide variety of CHD patients have CM abnormalities along with low nNO level and these are

associated with increased respiratory symptoms as well as adverse post-operative outcomes.

Our studies support a possible underlying mechanism leading to development of CHD involving

mutations in genes relating to cilia structure or function. Screening patient with CHD for ciliary

dysfunction might allow for prophylactic treatment of such patients in order to decrease their risk

of post-operative infection and complications, which typically have been attributed to their CHD

in the past.

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185

REOPERATIVE CARDIAC SURGERY IN ADULT CONGENITAL HEART DISEASE

PATIENTS

B.N. Mora Division of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota, USA

Objectives: To discuss the spectrum of anomalies which require reoperative cardiac surgery in the

adult congenital heart disease (ACHD) patient.

Background: There are >1,000,000 ACHD patients in North America. Cardiac surgery in those is

divided into cases involving great complexity (e.g. cyanotic lesions, single ventricle, double-outlet

ventricle), moderate complexity (e.g. anomalous pulmonary venous drainage, atrioventricular

septal defects, coarctation, Ebstein’s, right ventricular (RV) or left ventricular (LV) outflow tract

obstruction, non-secundum atrial septal defect (ASD), pulmonary regurgitation (PR) or stenosis,

tetralogy of Fallot, complicated ventricular septal defect (VSD)), and simple complexity (e.g.

isolated congenital valve stenosis or insufficiency, simple VSD, secundum ASD).

Results: The majority of reoperations for ACHD patients involve reoperative valve replacement,

especially in the pulmonary position. Often, more than one valve is addressed at reoperation, the

most common being pulmonary valve replacement and tricuspid valve repair. Pulmonary valve

replacement is indicated for severe PR with symptoms, RV dysfunction/enlargement, arrhythmias,

or significant tricuspid insufficiency. Indications for reoperative valve repair or replacement

include worsening CHD valvar stenosis or regurgitation, which should undergo valve therapy as

in patients with non-congenital valve disease. Patients may also present with subaortic stenosis,

and should undergo resection if operative criteria are met. Other operations include reoperations

on the RV outflow tract for obstruction from severe valvar obstruction who require surgery if

percutaneous therapy is contraindicated. Subvalvar stenosis, supravalvar stenosis and double-

chambered RV require surgery. Only a minority of single ventricle patients will require reoperation

in adulthood, most commonly either implantation of an epicardial pacemaker/defibrillator, or heart

transplantation.

Conclusions: Reoperative cardiac surgery for ACHD patients involves a wide spectrum of lesions

with established indications and reasonable morbidity and mortality. As more CHD patients

survive into adulthood, the variety of reoperative cardiac surgical repairs will increase in

complexity.

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186

CHILDREN WITH CONGENITAL HEART DISEASE MAY BE AT RISK FOR

PREMATURE ATHEROSCLEROSIS IN SPITE OF SUCCESSFUL BIVENTRICULAR

REPAIR C. Lilje1,3, B. Finckh2, I. Boeters3, T. Heitzer3, A. Kohlschuetter2, J. Weil3

1. Louisiana State University Health Sciences Center, New Orleans, LA, USA

2. University Medical Center Hamburg-Eppendorf, Hamburg, Germany

3. University Heart Center Hamburg-Eppendorf, Hamburg, Germany

Objective: To prospectively assess the risk for premature vascular aging in asymptomatic children

with congenital heart disease (CHD at least 5 years after successful surgical repair.

Background: Autopsy studies have shown that atherosclerotic changes can be found in early

childhood. Oxidative stress, endothelial dysfunction, and vessel wall proliferation have been

associated with key initiating events in developing vascular disease. Little is known about the

vascular status of children with congenital heart disease CHD years after successful biventricular

repair in infancy.

Probands and methods: 32 pediatric patients with CHD and 33 controls (11 age-matched children

and 22 young adults), matched for sex, race, and BMI. The CHD group comprised Ventricular

Septal Defects (5), Tetralogy of Fallot (10), and Transposition of the Great Arteries (17). Plasma

markers for pro-/antioxidative balance included homocystein, malondialdehyde, vitamin C, TRAP

assay, and sulfhydryl groups. Brachial flow mediated vasodilation (FMD) and Intima-Media

Thickness (IMT) were analyzed using high-resolution external ultrasound. Excluded were

individuals with standard atherosclerosis risk factors such as smoking, diabetes, hypertension,

obesity, and dyslipidemia.

Results: Compared to pediatric controls, CHD patients – like adult controls – had higher

homocystein levels, lower vitamin C levels, and impaired FMD. IMT was only increased in adult

controls.

Conclusion: In teenage patients with biventricular CHD, successfully repaired in infancy, evidence

was found for oxidative stress endothelial dysfunction. This population may be at risk for

premature vascular aging.

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CARDIAC STRUCTURE AND FUNCTION IN FAILING AND NON-FAILING HEARTS

187

AGING, EXTRACELLULAR MATRIX AND HEART FAILURE: 2015

B.I. Jugdutt


The aging population with heart failure (HF) is increasing worldwide. Hypertension (HTN) and

myocardial infarction (MI) are the two main comorbidities leading to HF in the elderly (age ≥ 65

years). Aging is progressive and results in cardiovascular changes that lead to an aging phenotype

and negatively impact disease expression and response to therapy. Aging-related changes

contribute to adverse cardiac remodeling and HF with preserved ejection fraction (HF/PEF). HTN

also leads to HF/PEF whereas MI leads to HF reduced EF (HF/Low-EF). Aging and concomitant

HTN or MI accelerates the march to HF. The cardiac extracellular matrix (ECM) is critical for

maintaining cardiac shape/function. A key mechanism in the development and progression of HF

due MI and HTN involves adverse cardiac ECM remodeling. Disruption of the ECM network and

dysregulation of ECM homeostasis and metabolism result in adverse cardiac remodeling with

shape deformation and dysfunction that lead to HF, disability and death. Aging-related cardiac

remodeling with superimposed progressive left ventricular remodeling leading to HF/PEF or

HF/Low-EF in older patients is a persistent problem that has important therapeutic implications.

Studies suggest that in the elderly, novel pathways can be targeted for optimizing therapy in HF/Low-

EF post-MI and HF/PEF post-HTN. Therapeutic strategies that include targeting of adverse cardiac

ECM remodeling could prevent/limit/reverse progression to HF in aging patients.

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188

THE POST-PERICARDIECTOMY SYNDROME: PREVENTION AND

MANAGEMENT

B.D. Hoit

University Hospitals Case Medical Center, Cleveland OH, USA

The post-pericardiotomy syndrome (PPIS) and post-operative effusions affect over one third of

patients after cardiac surgery, and while they often have little impact on management, they may

lead to prolonged hospital stay, readmissions, and the need for pericardial drainage. Treatment of

the PPIS is similar to other types of acute pericarditis, and includes the initial use of aspirin or

nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine, with steroids reserved for

refractory or relapsing cases. Colchicine is the only therapy that has been demonstrated to

significantly reduce the incidence of post-cardiac injury syndrome following cardiac surgery, but

there are conflicting data suggesting that colchicine use postoperatively may be associated with an

increased number of adverse medication-related side effects. Two randomized, double-blind trials

have evaluated colchicine in this regard. Data from the Colchicine for the Prevention of Post-

pericardiotomy Syndrome (COPPS)-1 trial of 1 month post-operative treatment with colchicine

begun on postoperative day 3 significantly reduced the occurrence of the PPIS at 12 months

(relative risk 0.42, 95% CI 0.24-0.73) with similar rates of side effects, primarily related to

gastrointestinal intolerance in the colchicine and placebo groups. Data from the COPPS-2 trial of

1 month post-operative treatment with weight-adjusted colchicine beginning 48 to 72 hours prior

to surgery significantly reduced the occurrence of the PPIS at three months (relative risk 0.66, 95%

CI 0.45-0.96). However, unlike the COPPS-1 trial, treatment with colchicine was associated with

significantly more gastrointestinal adverse effects. A 1-month course of colchicine to reduce the

risk of developing PPIS and its potential complications should be weighed against the risk of

medication-related side effects. In those who choose not to take colchicine, the early recognition

and treatment of PPIS is important.

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189

CARDIAC FIBROSIS IN HEART FAILURE

A.J. Taylor

Department of Cardiovascular Medicine, Alfred Hospital and BakerIDI Heart and Diabetes

Institute, Melbourne, Australia

Myocardial fibrosis is a fundamental event in the development of cardiac failure, and is a common

feature in all patients with advanced cardiac failure regardless of the aetiology of cardiomyopathy.

Increasing myocardial fibrosis results in progressive deterioration of myocardial function, with

more extensive myocardial fibrosis identified histologically in the hearts of patients with advanced

heart failure. Regional myocardial fibrosis, whilst most commonly observed in ischaemic

cardiomyopathy, is present in a broad range of non-ischaemic cardiomyopathies. With the advent

of cardiac magnetic resonance (CMR) imaging, identification and quantification of regional

fibrosis with late gadolinium enhancement (LGE) has stimulated research into the diagnostic and

pathological role of regional cardiac fibrosis in cardiomyopathy. Whilst initially focused on its

role in the identification of myocardial scar in ischaemic heart disease, the presence and

distribution of LGE has improved diagnosis across a range of cardiomyopathies, including

sarcoidosis and amyloidosis. Regional fibrosis is also now thought to play a significant role as a

substrate for malignant ventricular arrhythmia, and its presence has been linked to pathological

cardiac remodelling and adverse prognosis. Diffuse myocardial fibrosis is observed in all forms of

advanced cardiomyopathy, and can now be assessed semi-quantitatively with CMR T1 mapping.

Prior studies using either contrast-enhanced or non-contrast T1 mapping have demonstrated strong

correlations with myocardial T1 time and the extent of diffuse fibrosis histologically. Using CMR

T1 mapping, a relationship between interstitial fibrosis and cardiac stiffness has been

demonstrated, where it is likely to play a significant mechanistic role in heart failure with preserved

ejection fraction (HFPEF). Additional studies have demonstrated the utility of CMR T1 mapping

in the differentiation of cardiomyopathy, and the extent of diffuse fibrosis identified by CMR has

been shown to be a strong, independent predictor of adverse outcome in heart failure.

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190

GENETIC EPIDEMIOLOGY OF LEFT VENTRICULAR HYPERTROPHY

J.N. Bella

Bronx-Lebanon Hospital Center, Bronx, NY, USA

Left ventricular (LV) hypertrophy is a strong independent predictor of increased cardiovascular

morbidity and mortality in clinical and population-based samples. Clinical and hemodynamic

stimuli to LV hypertrophy induce not only an increase in cardiac mass and wall thickness but also

a fundamental reconfiguration of the protein, cellular and molecular components of the

myocardium. Several studies have indicated that LV mass is influenced by genetic factors. The

substantial heritability for LV mass in population-based samples of varying ethnicity indicates

robust genetic influences on LV hypertrophy. Genome-wide linkage and association studies in

diverse populations have been performed to identify genes influencing LV mass, and although

several chromosomal regions have been found to be significantly associated with LV mass, the

specific genes and functional variants contained in these chromosomal regions have yet to be

identified. In addition, multiple studies have tried to link single-nucleotide polymorphisms (SNPs)

in regulatory and pathway genes with common forms of LV hypertrophy, but there is little

evidence that these genetic variations are functional. Up to this point in time, the results obtained

in genetic studies are of limited clinical value. Much of the heritability remains unexplained, the

identity of the underlying gene pathways, genes, and functional variants remains unknown, and

the promise of genetically-based risk prediction and personalized medicine remain unfulfilled.

However, molecular biological technologies continue to improve rapidly, and the long-term

potential of sophisticated genetic investigations using these modern genomic technologies,

coupled with smart study designs, remains intact. Genetic investigations offer much promise for

future prevention, early intervention and treatment of this major public health issue.

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191

THE ROLE OF RIGHT VENTRICLE ON HEART FAILURE PROGRESSION

C. Chrysohoou

Cardiologist University of Athens, Greece

Right ventricle (RV) has become a priority in cardiovascular research, playing a significant role in

the prognosis of patients with heart failure. Both ventricles share similarities but also many

differences. In the embryological origin, the shape, myocardial characteristics and architecture,

physiological pump conditions and flow characteristics. The motion of tricuspid annuls plays a

significant role for the filling of right ventricle; while isovolumic contraction and relaxation times

are rather shortened. In high pressure conditions, those times are prolonged and the pressure-

volume curve of the right ventricle becomes similar with that of the left ventricle. Beyond those

morphological differences, there are also molecular differences between the left and right

ventricles in response to adverse loading, with the right ventricle showing less response to a1

adrenergic stimulation, BNP infusion, compared to the left ventricle. Right ventricle pacing leads

to little detectable mechanical activity (measured as developed pressure) in the left ventricle.

Reducing left ventricle volume from its optimal volume to zero causes a 5.7% decrease in right

ventricle developed pressure, whereas ligating the coronary supply to the left ventricle free wall

results in an additional 9.3% decrease in right ventricle developed pressure; while >50% of the

normal right ventricle mechanical work may be generated by left ventricle contraction and that the

left ventricle free wall plays a pivotal role in right ventricle function. The prevalence of RV

dysfunction in patients with reduced left ventricle left ejection fraction reaches almost 73% when

assessed by Tissue Doppler. In dilated cardiomyopathy right ventricular ejection function is as

complementary, independent prognostic factor, though significant correlations exist between both

left and right parameters of ventricular function and has been associated with overall survival more

accurately than VO2max in both severe and moderate heart failure. Right ventricular failure is a

major contributor of significant morbidity and mortality after left ventricular assist devices

placement. The complex pathophysiology of right ventricular failure, which could potentially be

related to RV myocardial dysfunction, interventricular dependence, and right ventricular afterload,

has led to inconsistencies in predicting risk factors for right ventricle dysfunction. There are several

therapeutic interventions aiming to improve right ventricular performance, even in the case of heart

failure with preserved ejection fraction. Among all imaging modalities, magnetic resonance and

Doppler echocardiography have shown significance on visualizing right ventricular function and

clinical prognosis

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192

EVOLVING UNDERSTANDING OF STRESS CARDIOMYOPATHY

A. Chockalingam

Division of Cardiovascular Medicine, University of Missouri, Columbia, MO, USA

Stress cardiomyopathy (SC), also called Takotsubo cardiomyopathy, is increasingly diagnosed

world over. ER physicians, Internists, Intensivists and anesthesiologists increasingly encounter SC

patients presenting with angina, heart failure or arrhythmia. Initially, most patients were diagnosed

in the catheterization lab when coronary angiograms were normal in STEMI settings. With

increasing awareness among various providers and the wide proliferation of echocardiography,

majority of this diagnosis is now made in critically ill hospitalized medical and surgical patients.

The widely accepted Mayo criteria for diagnosis requires angiographic proof of normal coronaries.

We have published a non-invasive echo based diagnostic algorithm that is applicable widely but

especially suitable for the critically ill patients who are not candidates for catheterization or

revascularization due to co-morbidities. Typical mental or physical stresses, ECG ischemia and

subtle enzyme elevation raise the suspicion of ‘possible SC’. The first test can be an

echocardiogram with careful assessment of LV wall motion. Disproportional significant LV

dysfunction and regional abnormalities not conforming to a single coronary territory or

characteristic apical ballooning raises this diagnosis to ‘probable SC’ at presentation. While

unstable or critical coronary disease excludes SC, in a significant portion of the people with this

diagnosis, we detect coincidental mild to moderate CAD during catheterization. If symptoms or

ECG suggest STEMI, catheterization and revascularization should not be delayed. In many

situations, especially in critically ill medical and surgical patients, catheterization is deferred for a

few days for medical stabilization. The most specific diagnostic criterion and unique feature of SC

is the spontaneous complete normalization of LV function and wall motion; this typically occurs

within a few days requiring only supportive care. Thus, repeat echo after 3-5 days of presentation

may demonstrate this recovery of LV function, facilitating the diagnosis of ‘definite SC’. Clinical

suspicion and echocardiography can optimize SC care.

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193

MYOCARDIAL SEGMENTAL THICKNESS VARIABILITY ON CMR

DISTINGUISHES ISCHEMIC AND NON-ISCHEMIC DILATED CARDIOMYOPATHY

M. Singh, M. Bhullar, A. Samim, M. Srikanth, C. Katikireddy

Division of Cardiology, UCSF Fresno, Fresno, CA, USA

Objective: We hypothesized that in patients with dilated cardiomyopathy of unknown etiology, segmental

wall thinning from infarcted or hibernating myocardium on CMR (cardiac magnetic resonance) imaging

can distinguish ischemic cardiomyopathy (ICM) from non-ischemic cardiomyopathy (NICM).

Background: Distinction of dilated ICM from NICM is critical, however can be challenging by noninvasive

testing.

Methods: We retrospectively identified 72 consecutive dilated cardiomyopathy patients of unknown

etiology referred for CMR over a two-year period. CMR protocol included 2D steady state free precession

(SSFP) cine, perfusion, delayed contrast enhancement (DE) imaging and additional sequences as required.

We defined segmental wall thickness variability (differential wall thickness) as >50% difference in end

systolic thickness, between the segments (a minimum of two) of any two different coronary territories.

CMR characteristics of cardiac chamber morphology, differential wall thickness (DW), wall motion,

valves, pericardium, myocardial perfusion and DE were compared between the ICM and NICM (as

confirmed by coronary angiography) using χ2 and ANOVA. Their diagnostic value was assessed using

ROC analysis.

Results: A total of 30% had NICM. Mean age, left ventricular size and ejection fraction of the study

population were 58 years, 6.2 cm, and 28%, respectively. No significant difference was observed between

the ICM and NICM among baseline characteristics and 13 of the 15 CMR markers. DW and DE imaging

on CMR differentiated ICM from NICM. DW outperformed DE in diagnosing ICM with a sensitivity and

specificity of 94% and 99% versus 89% and 74% respectively (figure).

Conclusions: DW resulting from thinning of infarcted or hibernating myocardium can accurately

differentiate ICM from NICM where segmental wall thickness is uniform. As DW can be assessed by CMR

with no IV contrast, it is especially useful in patients where IV Gadolinium is contraindicated.

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194

ASSESSMENT OF RIGHT VENTRICULAR INVOLVEMENT IN TAKOTSUBO

CARDIOMYOPATHY P. Shah, R.C Van Woerkom, J.W. Schleifer, F.D. Fortuin, K. Chandrasekaran

Mayo Clinic Arizona, Phoenix, Arizona, USA

Background: Although left-ventricular (LV) involvement in Takotsubo cardiomyopathy (TC) is well

defined, right ventricular (RV) involvement may be under reported.

Objective: Compare co-morbidities, echocardiographic findings, and the clinical course of patients

diagnosed with TC with RV involvement to those patients without RV involvement. Methods: A

retrospective chart review identified 58 patients admitted from January 2006 to November 2011 with TC

who underwent coronary angiography and had an absence of high grade coronary artery disease. LV

dysfunction and RV dysfunction was defined by standard American Society of Echocardiography

guidelines, and these guidelines were followed for analysis of the echo data. Both groups were compared

using an unpaired student t-test.

Results: The average age of the cohort was 70 years, 80% of which were female. Further findings are

reported in table 1. None of the patients died during the hospitalization.

Conclusions: Patients with TC and RV involvement were more frequently former tobacco users, had

numerically lower ejection fractions, increased frequency of ST-elevation, and a longer hospital stay. None

of these findings reached statistical significance; however, this may be secondary to our small cohort, which

is a limitation of this study. Further exploration of RV involvement in patients with TC is warranted.

Table 1. Co-morbidities, echocardiographic findings and clinical course of TC cases in those patients with,

and without, RV involvement. Values are mean (± standard deviation) unless otherwise noted. Percentages

are percent of the patient population RV dysfunction + LV

dysfunction (n=34)

LV dysfunction only

(n=24)

P value

Co-Morbidities

Hypertension 68% 71%

Diabetes Mellitus 21% 21%

Tobacco history 59% 42%

Current tobacco use 9% 13%

Echocardiography

LV ejection fraction .40 (±14) .45(±.14)

.17

Wall motion score 1.8 (±.4) 1.8(±.4) .43

Apical Left Ventricular

Variant

79% 75%

Mid-Left Ventricular Variant 21% 25%

Basal-Left ventricular variant 0 0

Clinical Course

CKMB 13.5(±16.4) 22.4(±34.6) .21

Peak Troponin .34 (±.45) .37 (±.4) .76

BNP 914 (±813.5) 1412 (±1481.7) .19

ECG ST Elevation 56 % 42 %

Average Length of

Hospitalization (days)

6.3 (±6) 5.4 (±6.5) .59

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195

DETERMINANTS OF LEFT VENTRICULAR RECOVERY IN STRESS

CARDIOMYOPATHY: A SINGLE CENTER EXPERIENCE M. Abbasi, H. Ismail, A. Alam, S. Singh, L. Boutis

Northshore Long Island Jewish Medical Center, Manhasset, NY, USA

Background: Stress cardiomyopathy (SC) has become an increasingly recognized syndrome

characterized by acute, transient systolic dysfunction of different segments of the left ventricle

(LV) in response to emotional or physical stress. Most patients recover LV function, however,

there is insufficient evidence of what factors predict LV recovery.

Methods: We identified 46 patients (43 women, 3 men, age 68.6 ±15.8) who were admitted to our

institution between 2011-2014 with a diagnosis of SC. We analyzed clinical profiles, data, and

outcomes of the patients that would help predict recovery of LV function. Statistical significance

was determined by the unpaired student's t-test and the Chi squared test corrected by Fisher's exact

using commercially available software (p<0.05).

Results: Five out of 46 patients had no recovery of initial LV dysfunction with an average follow-

up ejection fraction (EF) of 36.6% versus 59.2% in recovered patients. Non-recovered patients

were more likely to be diabetic (40% vs 7.3%, p = 0.02), have greater initial creatine kinase-

myocardial band isoenzyme (CK-MB) (35.62 ± 21.5 vs 16.25 ± 2.0, p = 0.04), and discharge

troponins (0.69 ± 0.29 vs 0.32 ± 0.05, p=0.04). Treatment with beta blockade was also found to be

associated with recovery (95.1% vs 60%, p = 0.009), while use of other cardio-protective drugs

showed no significant difference. Factors such as mean arterial pressure, treatment with inotropes,

LV hypertrophy on echocardiography, and peripheral vascular disease, did not meet statistical

significance (p<0.05), but did demonstrate a trend that may warrant further investigation.

Conclusion: In this study, we identified a number of factors predictive of poor LV recovery in

patients with SC. Knowledge of these factors would allow for better risk stratification and help

guide more aggressive therapy potentially avoiding permanent LV dysfunction.

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ADVANCES IN ARRHYTHMIA DETECTION, PREVENTION AND TREATMENT

196

PREDICTING READMISSION AFTER IMPLANTABLE CARDIOVERTER

DEFIBRILLATOR USING A RISK MODEL S. Oliver-McNeil1,2, T.N. Templin1, D.E. Haines1

1. Wayne State University College of Nursing, Detroit, MI, USA

2. Beaumont Health, Royal Oak, MI, USA

Objectives: The goal of this study was to implement the ICD risk stratification model developed

through NCDR data to determine if patients could be identified for 30-day readmission.

Background: Previous analysis of the National Cardiovascular Data Registry (NCDR) ICD

database identified clinical risk factors for procedure-related complications.

Methods: Patients scheduled to undergo ICD implantation were prospectively identified.

Preoperative NCDR ICD risk score was calculated by assigning points for age > 70 years; female

sex; prior valve surgery; chronic lung disease; dual or biventricular device; history of atrial

fibrillation/flutter; NYHA class II-IV heart failure; non-elective hospitalization; and BUN >30;

and re-implantation other than elective generator change. A logistic regression model determined

the association of variables and pre-procedure risk to all-cause 30-day readmission rate.

Results: 182 consecutive patients undergoing ICD implantation were assessed. Mean age was 69

years (SD=11.00), with 72% (n=131) of the group consisting of men. The 30-day readmission rate

was 17.6%. Four variables from the ICD Adverse Outcome Risk Model, (BUN >30, history of

lung disease, NYHA Class IV and device implant during an inpatient hospital stay) were identified

as predicative of 30-day readmission. Patients with a combination of 2 or more out of the 4 risks

were more likely to be readmitted (Hosmer-Lemeshow test (χ2 (8) = 5.20, P = .74), c-statistic =

.71, and Nagelkerke R square = 0.15).

Conclusion: In a typical group of patients receiving ICD implant, the four variables were predictive

of all-cause 30-day readmission rate. The risk factors identified were similar to previous studies.

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197

LONG-TERM EVALUATION OF BIOTRONIK LINOX AND LINOXSMART ICD

LEADS E.D. Good6, I. Cakulev1, M. Orlov2, D. Hirsh3, H. Bloom4, J. Simeles5, K. Mohr5

1. University Hospitals of Cleveland, Cleveland, OH, USA

2. Caritas St. Elizabeth's Boston, Boston, MA, USA

3. Emory University, Atlanta, GA, USA

4. Emory University and Atlanta VA Medical Center, Atlanta, GA, USA

5. BIOTRONIK, Portland, OR, USA

6. University of Michigan, Ann Arbor, MI, USA

Introduction: Spurred by a rash of recent ICD lead failures and advisories, systematic assessment

of post-implant lead performance has risen to the level of imperative in the collective conscience

of both physicians and industry, alike. GALAXY (NCT00836589) and CELESTIAL

(NCT00810264) are ongoing multi-center, prospective, non-randomized observational studies

being used to effect such evaluation by analysis of long-term safety and performance data of

BIOTRONIK leads.

Methods: ICD and CRT-D pts are being followed for lead performance and safety of the Linox

and Linoxsmart ICD leads for 5 yrs post-implant. All procedural and system-related adverse events

(AEs) are assessed at each follow-up along with lead electrical parameters. An independent CEC

of 5 EPs adjudicates all AEs to determine AE category and lead relatedness. Adjudicated AEs are

then categorized per ISO 5841-2 (3rd edition). Figure 1 displays a Kaplan-Meier actuarial graph

by Linoxsmart and Linox ICD model groups.

Results: A total of 3915 leads were implanted in 3833 pts (73.0% male, mean age 67.0 ± 12.2 yrs)

at 146 US centers. The estimated cumulative survival probability is 97.3% at 5 yrs after implant

for Linox leads and 98.3% at 4 yrs after implant for Linoxsmart leads. The most common AEs

were oversensing (19, 0.49%), failure to capture (10, 0.26%), and conductor fracture (9, 0.23%),

abnormal pacing impedance (7, 0.18%), lead dislodgement (7, 0.18%), insulation breach (5,

0.13%).

Conclusion: Linox and Linoxsmart ICD lead-related AEs are rare; and, lead electrical performance

and cumulative survival probability are excellent.

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198

POTENTIAL OF AMINOGLYCOSIDE ANTIBIOTIC GENTAMICIN TO CORRECT

FUNCTIONAL EXPRESSION OF TRUNCATED HERG CHANNELS LINKED TO

LONG QT SYNDROME, SYNCOPE AND UNEXPECTED SUDDEN DEATH G.L. Li1 , W.Q. Han1, J.E. Wu1, A.F. Zhang2, X. He1, Y. Lv3, G. Cheng3, R Shi1, C.F. Sun1

1. Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi’an Jiaotong

University College of Medicine, Xi'an, Shaanxi, China

2. Department of Cardiovascular Medicine, the Second Affiliated Hospital of Xi’an Jiaotong

University College of Medicine, Xi'an, Shaanxi, China

3. Department of Cardiovascular Medicine, Shaanxi Provincial People’s Hospital, Xi'an,

Shaanxi, China

Background: Long QT syndrome (LQTS) refers to a group of genetically cardiac rhythm disorders

Mutations in the human ether-a-go-go-related gene (hERG) are linked to LQTS type 2 (LQT2),

the most common form in China. A compound mutation (L539fs/47-hERG) responsible for

truncated hERG channels was identified in a Chinese family experiencing LQTS, syncope and

unexpected sudden death.

Objective: The present study aimed to evaluate the potential of gentamicin on the compound

mutation L539fs/47-hERG bearing premature termination codon.

Methods: The L539fs/47-hERG and WT plasmids were transfected into the HEK293 cells to

simulate heterozygous mutant. Whole cell patch-clamp technique were used to measure hERG

currents in control conditions and exposed to gentamicin. Additionally, laser confocal scanning

microscopy was used to evaluate the membrane distribution of hERG channel protein using a green

fluorescent protein tagged to the N-terminus of hERG.

Results: After cells were cultured in the presence of 400 g/ml gentamicin for 24 h and then cultured

in drug-free drug-free MEM at 37℃ for 1 hour to washout the drugs, the maximal density of tail

currents in cells expressing WT in control conditions and exposed to gentamicin were 54.86±

2.098 and 64.86±3.328, respectively, corresponding an increasing effect of 18.2%. The

counterparts of heterozygous mutant (WT+L539fs/47-hERG) were and 22.93±0.6733 pA/pF and

37.34±2.401 pA/pF, respectively, the increasing effect is 62.8%. Additionally, gentamicin results

in an obvious increase of hERG channel protein expression on the cell membrane and improves

the retention of hERG channel proteins in the endoplasmic reticulum in cells expressing

heterozygous mutant.

Conclusion: The function and expression of the truncated HERG channels due to a heterozygous

mutation (WT+L539fs/47-hERG) can be partially corrected by gentamicin. This suggests the

possibility to explore relevantly therapeutic strategies to benefit LQTS individuals.

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199

SURVEY OF DISPATCHER-ASSISTED CARDIOPULMONARY RESUSCITATION

AFTER IMPLEMENTATION OF CONTINUOUS QUALITY IMPROVEMENT

PROJECT IN ISHIKAWA PREFECTURE H. Inaba1, Y. Tanaka1, T. Kamikura1, Y. Wato2, T. Nishi1, A. Funada1

1. Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa, Japan

2. Department of Emergency Medicine, Kanazawa Medical University, Uchinada, Ishikawa,

Japan

Background: In 2007, the Ishikawa Medical Control Council initiated the continuous quality

improvement (CQI) project for telephone-assisted cardiopulmonary resuscitation (telephone-

CPR), which included instruction on chest-compression-only CPR, education on how to recognise

out-of-hospital cardiac arrests (OHCAs) with agonal breathing, emesis and convulsion,

recommendations for on-line or redialling instructions and feedback from emergency physicians.

We investigated the sensitivity and specificity of our new DA-CPR protocol after CQI project for

achieving implementation of bystander CPR in out-of-hospital cardiac arrest victims not already

receiving bystander CPR.

Methods and Results: Fire departments prospectively collected the data. The incidence of

telephone-CPR and bystander CPR significantly increased after the project (from 42% to 62% and

from 41% to 56%, respectively). After the project (2009-2011), DA-CPR was attempted in 2747

patients; of these, 417 (15.2%) did not experience cardiac arrest. The sensitivity and specificity of

the 2007 protocol versus estimated values of the previous standard protocol were 72.9% versus

50.3% and 99.6% versus 99.8%, respectively. We identified key words that may be useful for

detecting out-of-hospital cardiac arrest. Multiple logistic regression analysis revealed that the

occurrence of cardiac arrest after an emergency call (odds ratio, 16.85) and placing an emergency

call away from the scene of the arrest (odds ratio, 11.04) were potentially associated with failure

to provide DA-CPR. Furthermore, at-home cardiac arrest (odds ratio, 1.61) and family members

as bystanders (odds ratio, 1.55) were associated with bystander noncompliance with DA-CPR. No

complications were reported in the 417 patients who received DA-CPR but did not have cardiac

arrest.

Conclusions: Our 2007 protocol is safe and highly specific and may be more sensitive than the

standard protocol. Understanding the factors associated with failure of bystanders to provide DA-

CPR and implementing public education are necessary to increase the benefit of DA-CPR.

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200

IDEAL TARGET TEMPERATURE DURING THERAPEUTIC HYPOTHERMIA

AFTER OUT-HOSPITAL CARDIAC ARREST A.L. Schenone1, A. Cohen1, G. Patarroyo2, L. Harper1, M. Shishehbor3, A. Duggal2

1. Internal Medicine, Cleveland Clinic, Ohio, USA

2. Pulmonary and Critical Care Department, Cleveland Clinic, Ohio, USA

3. Heart and Vascular Institute, Cleveland Clinic, Ohio, USA

Background: Out-hospital cardiac arrest (OHCA) carries a high mortality (~60%). Therapeutic

hypothermia is the first intervention to improve outcomes after OHCA. Nevertheless, there is no

conclusive ideal temperature to cool patients. Formal recommendation still proposes 32-34C as

target temperatures. This study aims to determine the effect modification of different temperatures

during therapeutic hypothermia on outcomes using pooled data from existing literature.

Methods: We identified studies by searching electronic databases (Medline, Embase, and Cochrane

Library). We included randomized controlled trials (RCTs) and cohort studies describing hospital

mortality and neurological outcomes of comatose survivors of OHCA after therapeutic

hypothermia. Additional eligibility criteria included: age >15 years old, any initial rhythm,

reported achieved temperature during cooling. Eligible studies underwent data extraction and

quality assessed for risk of bias. Data from hypothermia receiving groups, with acceptable risk of

bias, were pooled and grouped by achieved target temperature. Outcomes were contrasted across

temperatures (32°C, 33°C, 34°C, 35°C, and 36°C).

Results: The search strategy identified 32,275 studies. Yet, 24 studies met eligibility criteria,

accounting for 33 hypothermia groups. Pooled data accounted for 4420 patients with mean age of

60 years, and 77% male proportion. Total of 20 cooling arms enrolled patients regardless of initial

rhythm, while 9 and 4 included either shockable or non-shockable rhythm respectively. Shockable

rhythms accounted for 70% of all cardiac arrests, while a cardiac cause triggered 80% of arrests.

Average downtime was 25.6 minutes. Overall, mortality around discharge was 43.4% with rate of

good outcome of 43%. There was no difference in hospital mortality or good neurological

outcomes across cooling temperatures after OHCA (p=0.99 and (p=0.89 respectively).

Conclusion: After pooling data from existing literature, therapeutic hypothermia after out-hospital

cardiac arrests seems to provide same benefit on mortality or good neurological outcomes at

discharge across different target temperatures (32°C-36°C).

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201

IMPACT OF CONDUCTION VELOCITY ON LOCAL CAPTURE OF ATRIAL

FIBRILLATION INDUCED BY RAPID PACING

N. Virag1, A. Luca2, T. Kallmyer3, A. Rusu2, J-M. Vesin2

1. Medtronic Europe, Tolochenaz, Switzerland

2. Swiss Federal Institute of Technology, Lausanne, Switzerland

3. Medtronic, Tempe, AZ, USA

Objectives: Rapid pacing of atrial fibrillation (AF) can induce local atrial capture. The present

model-based study investigated the impact of atrial tissue conduction velocity on AF capture

ability during rapid septal pacing.

Methods: The AF model combined a membrane kinetics model with geometry based on computed

tomography of AF patients. Conduction velocity was varied ±20% over a baseline AF model based

on multiple reentrant wavelets. Rapid pacing of AF was applied from the septum for 50s with

pacing cycle length (PCL) computed as percent of mean AFCL. Analysis of 24 electrode pairs

evenly distributed on the atrial surface yielded percentage of captured tissue (CL within ±5% of

PCL). Capture window was the range of PCL with capture > 50%. Reentrant wavelets quantity

(#W) was computed before and during pacing. Optimal PCL was leading to the highest capture.

Results were averaged on 10 AF simulations.

Results: AFCL did not change significantly with conduction velocity, and optimal PCL was

comparable for the 3 velocity values. An increase/decrease in velocity reduced/extended the

capture window. The maximum capture was obtained with a decreased conduction velocity even

if #W was higher prior to pacing.

Conclusions: Changes in atrial tissue conduction properties produced significant differences in

rapid pacing outcomes, suggesting that different types of AF may respond differently to

therapeutic pacing. Optimal capture parameters depended on AF dynamics but not AFCL.

Atrial Tissue AF Capture Capture at Optimal PCL

Conduction

Velocity

AFCL (ms) #W

AF

Capture

Window

Optimal

PCL

Captured

Tissue

#W

Capture

Baseline-20% 81±23 12.9±3.3 75-95% 79% AFCL 98% 3.5±2.5

Baseline 76±21 10.6±3.1 83-99% 87% AFCL 80% 5.8±2.2

Baseline+20% 75±20 8.1±2.7 83-93% 87% AFCL 65% 6.8±2.1

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202

LATE RE-CONDUCTION SITES IN THE SECOND SESSION AFTER PULMONARY

VEIN ISOLATION USING ADENOSINE-PROVOCATION FOR ATRIAL

FIBRILLATION K. Kaitani1, A. Kobori2, T. Kurotobi3, K. Okajima4, T. Yao5, Y. Nakazawa6

1. Tenri Hospital, Tenri, Nara, Japan

2. Kobe Center General Hospital, Kobe, Hyogo, Japan

3. Shiroyama hospital, Habikino, Osaka, Japan

4. Hyogo Prefectural Himeji Cardiovascular Center, Himeji, Hyogo, Japan

5. Okamura Memorial Hospital, Suntou, Shizuoka, Japan

6. Shiga University of Medical Science, Otsu, Shiga, Japan

Aims: Intravenous adenosine triphosphate (ATP) administration could reveal dormant conduction

(DC) gaps on the ablation line of a pulmonary vein isolation (PVI). We compared the ATP-

provoked DC sites in the initial PVI with the PV re-conduction sites in the second session in

patients with paroxysmal atrial fibrillation (AF).

Methods: We conducted a multicenter, observational study from a prospective registry undergoing

AF ablation. A total of 110 consecutive drug-refractory paroxysmal AF patients were enrolled in

this study. DC was detected by an ATP provocation of up to 40 mg during a continuous

isoproterenol infusion (0.5-2ƒÊg/ min). The DC sites at each of the right and left PVs were

precisely determined by using double spiral catheters under the guidance of a 3-dimensional

constructed anatomical mapping system.

Results: In the initial session, DC was observed in 35 patients (31.8%, 1.3 gaps /patient), and the

sites of the DC were commonly observed in the carina region (43.5%). AF recurrence was

confirmed in 33 patients (30.0%) during follow up (27.1 months), and a second session was

performed in 24 of 33 patients (70.6%). In the second session, the re-conduction sites were also

commonly observed in the carina region (59.5%).

Conclusions: The carina region was still a dominant re-conduction site even after the elimination

of any ATP-provoked DC in the index procedure.

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203

DOES THE DEVELOPMENT OF DEPENDENCY ON PACING IN PATIENTS WITH

IMPLANTED PACEMAKERS IMPACT ON SURVIVAL L. Ragupathi, P.U. Thanawala, J.A. Sendecki, R. Ho, D. Frisch, A. Greenspon,

B.B. Pavri

Thomas Jefferson University Hospital, Philadelphia, PA, USA

Introduction: Pacemaker (PM) dependency is defined as an absence of a stable, life sustaining

native rhythm without artificial pacing. The impact of PM dependency on survival is not well

described.

Methods: We reviewed 60 PM dependent patients (cases), and 60 age-and-sex matched patients

who were not PM dependent (controls). Device indications, comorbidities, time of PM

dependency, and last follow up or death were recorded.

Results: Mean age at implant was 70 (±12) years for cases and controls. There was no statistically

significant difference in the baseline prevalence of coronary artery disease, diabetes, or

hypertension at PM implant amongst cases and controls (all P=NS). Left ventricular ejection

fraction at implant was 57% in cases and 59% in controls (P=0.320). For cases, PM dependency

occurred a median 2.3 (mean=3.6) years after implant. Atrioventricular block was more common

in cases (48% vs. 17%, P=0.002) and sick sinus syndrome was more common in controls (37% vs.

10%, P=0.005). For cases, total follow up was a median 7.4 (mean=9.9) years and for controls,

total follow up was a median 4.4 (mean=5.3) years. There were 4 deaths in each group, none of

which were attributable to pacemaker malfunction. Patients who became PM dependent derived

an additional median 4.0 (mean=6.3) years of survival. There was no statistically significant

difference in overall survival of cases and controls (p=0.572).

Conclusions: The overall survival of PM dependent patients was comparable to age and sex

matched controls who were not PM dependent. The development of PM dependency does not

impart a worse prognosis. Given the aging world population and increasing rates of PM

implantation, this is clinically relevant information for patients and physicians.

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NOVEL DIAGNOSTIC METHODS AND IMAGING TECHNIQUES

204

COMPARISON OF LEFT VENTRICULAR EJECTION FRACTION VALUES

OBTAINED USING INVASIVE CONTRAST LEFT VENTRICULOGRAPHY, GSPECT

AND TWO-DIMENSIONAL ECHOCARDIOGRAPHY N. Garg1, R. Singh1, R. Garg1, V. Gupta3, T. Dresser2, K. Aggarwal, M. Alpert1

1. University of Missouri School of Medicine, Columbia, MO, USA

2. Harry S Truman Veterans Affairs Medical Center, Columbia, MO, USA

3. Borgess Medical Center, Kalamazoo, MI, USA

Background: Measurement of left ventricular ejection fraction (LVEF) provides valuable

diagnostic and prognostic information in patients with ischemic heart disease. LVEF is measured

using a variety of techniques including invasive contrast left ventriculography, gated single proton

emission computed tomography (gSPECT) and two-dimensional echocardiography (2DE). LVEF

measurement may be duplicated if the patient receives more than one of these tests. This may

increase risk and add cost to the evaluation. This study assesses the relation of these three

modalities to one another in the measurement of LVEF.

Methods: Retrospective chart review was conducted on patients with chest pain who underwent

LVEF evaluation using each of the aforementioned modalities using standard protocols within a

three month period not interrupted by acute coronary syndrome by percutaneous or surgical

coronary revascularization. Comparison of LVEF values between techniques was accomplished

using Pearson correlation coefficients. A p value <0.05 was required for statistical significance.

Results: LVEF was evaluated using all three modalities in 58 patients (all males) whose mean age

was 65 ± 10 years. Correlations and associated p values were as follows: invasive contrast left

ventricularography vs. gSPECT (r=0.80, p<0.001); invasive contrast left ventriculography vs. 2DE

(r=0.69, p<0.001); and gSPECT vs. 2DE (r=0.69, p<0.001).

Conclusion: LVEF measured using either gSPECT or 2DE significantly and strongly correlates

with LVEF measured using invasive contrast left ventriculography. Thus, if LVEF has been

obtained using either gSPECT or 2DE before cardiac catheterization, invasive contrast left

ventriculography need not be performed, thus reducing the cost of the procedure and the risk

associated with exposure to iodinated contrast media and fluoroscopy

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205

INFLUENCE OF ESTROGEN AND PROGESTIN THERAPY ON PROGRESSION OF

PERICARDIAL ADIPOSE TISSUE IN POSTMENOPAUSAL WOMEN F. von Ziegler1, M. Greif1, J. Schenzle1, H.C. Becker2,3, A. Becker1

1. Medical Clinic I, Department of Cardiology, Ludwig-Maximilians-University of Munich,

Munich, Germany

2. Department of Clinical Radiology, Ludwig-Maximilians-University of Munich, Munich,

Germany

3. Department of Radiology, Stanford School of Medicine, Stanford, CA, USA

Background: Prophylactic effect of postmenopausal hormone replacement therapy (HRT) on

coronary atherosclerosis remains controversial. We therefore examined the influence of a

combined estrogen/progestin therapy on progression of pericardial adipose tissue (PAT), which

reflects atherosclerotic burden of coronary arteries and is very sensible to changes in lipid

metabolism. Additionally extent of coronary calcifications (CAC) was determined.

Methods: We determined the extent of PAT and CAC in 244 women (age 58.0 ± 6.1 years, time

after menopause 4.8 ± 2.5 years, group I) at the beginning of HRT using multislice computed

tomography. For quantification volume of PAT in [ml] and volume score of CAC was calculated.

After an observation period of 3 years progression of PAT and CAC in a second scan was

evaluated. Results were compared to an age and risk factor adjusted group of postmenopausal

women without HRT (group II).

Results: No significant difference in PAT volume (121 ± 48 ml vs. 143 ± 43 ml, n.s.), CAC volume

score (59 ± 95 vs. 52 ± 88, n.s.), or risk factor distribution between both groups at study entry was

found. In 51 women of group I and 47 women of group II CAC were excluded on initial scan, n.s..

After a mean observation period of 35.7 ± 5.7 months increase of PAT volume (46 ± 22 ml vs. 79

± 36 ml, p < 0.01) between both groups was significantly different, whereas no significant

difference of CAC increase was determined (20 ± 24 vs. 23 ± 27, n.s.).

Conclusion: We observed a reduced progression of PAT in postmenopausal women under a

combined estrogen/progestin therapy compared to a matched group of women without HRT. Still

we could not find a reduced progression of CAC, indicating that PAT might be more sensitive to

short term changes of atherosclerotic burden.

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206

IMPACT OF HYPERLIPIDEMIA ON SUBCLINICAL ATHEROSCLEROSIS IN

ASYMPTOMATIC INDIVIDUALS E.H. Park1, G.M. Park1, T.S. Kim1, C.J. Kim1, J.S. Cho1, M.W. Park1, S.H. Her1,

J.B. Kwon2, Y.R. Cho3

1. Department of Cardiology, Daejeon St. Mary's Hospital, the Catholic University of Korea,

Daejeon, Korea

2. Department of Cardiothoracic Surgery, Daejeon St. Mary's Hospital, College of Medicine, The



Objectives: The purpose of this study was to investigate the impact of hyperlipidemia on the risk

of subclinical atherosclerosis in asymptomatic individuals.

Background: Little is known about subclinical atherosclerosis on coronary computed tomographic

angiography (CCTA) in asymptomatic individuals with hyperlipidemia.

Methods and Results: We analyzed 6,311 consecutive asymptomatic individuals aged 40 and older

with no prior history of coronary artery disease (CAD) who voluntarily underwent CCTA

evaluation as part of a general health examination between January 2007 and December 2011. The

mean age of the study population was 54.7±7.4 years, and 4,594 (72.8%) were male. Of the study

population, 1,970 (31.2%) had hyperlipidemia. After adjustment using age and gender

distributions from the 2010 South Korean population census, individuals with hyperlipidemia had

a significantly higher prevalence of plaque (standardized rate ratio [SRR], 1.30; 95% confidence

interval [CI]: 1.15–1.46; p<0.001), non-calcified plaque (SRR, 1.26; 95% CI: 1.05–1.52; p=0.013),

calcified plaque (SRR, 1.37; 95% CI: 1.18–1.58; p<0.001), mixed plaque (SRR, 1.17; 95% CI:

0.90–1.51; p=0.244), significant CAD (SRR, 1.65; 95% CI: 1.25–2.17; p<0.001), and significant

CAD in the in the left main or proximal left anterior descending artery (SRR, 2.13; 95% CI: 1.39–

3.28; p=0.001) compared with those without.

Conclusions: Hyperlipidemia was associated with subclinical atherosclerosis on CCTA. These

findings suggest the importance for control of lipid in asymptomatic individuals.

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207

ASSOCIATION OF GENDER AND BODY MASS INDEX WITH SUBCLAVIAN

INNOMINATE ARTERY TORTUOSITY IN PATIENTS UNDERGOING RIGHT

TRANS RADIAL CARDIAC CATHETERIZATION P.L. Nalabothu, N. Nannapaneni, G. Sireesha, S.A. Gilani, W. Khalife, A. Molham

University of Texas Medical Branch, Galveston, TX, USA

Background: Subclavian-innominate artery (SIA) tortuosity has been shown to be an independent

predictor of failure of Trans Radial (TR) cardiac catheterization. We sought to investigate the

factors related to the presence of SIA tortuosity in patients who underwent right TR cardiac

catheterization.

Methods: We did a retrospective study of who underwent right TR cardiac catheterization between

March 2011 and August 2014. The group consisted of 127 consecutive patients with SIA

tortuosity and 272 patients who did not have SIA tortuosity. Demographics and clinical

characteristics were compared between the two groups.

Results: Mean age of the patients (N=399) was 58.3±12.5 and 73% were males. When patients

were divided into two categories based on body mass index (BMI) patients with BMI more than

35 were more likely to have SIA tortuosity compared to patients with BMI less than 35 (62.7% vs

24.4% respectively, p<0.01). SIA tortuosity was more prevalent in males compared to females

(35.7% vs 21.2%, p<0.01). Age and height did not correlate significantly with the presence of SIA

tortuosity.

Conclusion: In patients who underwent right TR catheterization, SIA tortuosity was more likely

to be present in patients with BMI more than 35 and in males. Age and height did not correlate

significantly with the presence of SIA tortuosity

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208

THE USEFULNESS OF THE TDI TEI INDEX IN LEFT VENTRICULAR

FUNCTIONAL ASSESSMENT OF CHRONIC HEMODIALYSIS PATIENTS.

COMPARATIVE STUDY BEFORE AND AFTER DIALYSIS I.E Lagos, G.D. Spyromitros

General Hospital Katerini, Katerini, Greece

Objectives: The purpose of this study is to evaluate the effect of a dialysis session diastolic function

of the left ventricle using conventional sonographic markers (pulsed and tissue Doppler) and in

particular the use of TDI TEI index in adults with end-stage renal disease.

Background: 16 adults with chronic end-stage renal failure (9 men, 7 women, mean age 65 years)

underwent a standard dialysis session. The echocardiographic parameters studied were the velocity

of transmitral flow (MVpeak E), the ratio E / A, ratio E/E’, speeds at the tissue Doppler, the integral

of the flow velocity of the aortic valve (MeanPG) and TDI TEI index. The ultrasound data were

collected 20 minutes before and after dialysis and then compared.

Methods and Results: The dialysis resulted in reducing the speed of transmitral flow (MVpeak E,

p=0.005), a small decrease in the integral of the flow velocity of the aortic valve (MeanPG,

p<0.0001), reducing end diastole left ventricular filling pressures (p=0.05) and a reduction of end

diastole volume (p=0.001).No significant change was observed in the tissue velocities and in tissue

TEI index (TDI TEI INDEX) after dialysis.

Conclusions: Velocities TDI and TDI TEI index minimally affected by the reduction of preload

while the other indicators showed ultrasound change as inherent to the diastolic function, which is

directly dependent on the preload.

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ACUTE MYOCARDIAL INFARCTION / REPERFUSION THERAPY

209

IMPACT OF FACTORS ASSOCIATED WITH ARTERIAL AND/OR VENOUS

THROMBOSIS ON ACETYLSALICYLIC ACID AND CLOPIDOGREL RESPONSE

VARIABILITY IN PATIENTS PRESENTING WITH ACUTE CORONARY

SYNDROME E. Yalcinkaya1, A. Iyisoy2, T. Celik2, S. Kozan3, K. Kaptan4, A. Oztuna3, F.G. Oysul5,

S. Yasar2

1. Aksaz Military Hospital, Department of Cardiology, Mugla, Turkey

2. Gulhane Medical Faculty, Department of Cardiology, Ankara, Turkey

3. Gulhane Medical Faculty, Department of Medical Genetics, Ankara, Turkey

4. Gulhane Haydarpasa Training Hospital, Department of Hematology, Istanbul, Turkey, 5.

Gulhane Medical Faculty, Department of Public Health, Ankara, Turkey

Objectives: We sought to investigate whether the factors associated with arterial and/or venous

thrombosis influence response variability of acetylsalicylic acid and clopidogrel loading doses in

patients presenting with acute coronary syndrome (ACS) and those undergoing percutaneous

coronary intervention (PCI).

Methods: We analyzed the data of 166 patients presenting with ACS and those undergoing PCI.

Clinical data included assessments of genetic polymorphisms (angiotensin converting enzyme-

ACE I/D, Prothrombin G20210A, Factor V R506Q and methylenetetrahydrofolate reductase-

MTHFR C677T) and haematological factors (thrombin activatable fibrinolysis inhibitor-TAFI

activity, von Willebrand Factor antigen-vWF:Ag, Factor VIII, protein S, protein C activity and

antithrombin 3-AT 3 activity). Results: In multivariate regression analysis, ACE D/D

polymorphism (OR 2.369, p=0.043), TAFI levels (OR 1.017, p<0.001) and vWF:Ag levels (OR

1.014, p=0.003) were found as independent variables, which had statistically significant effects on

clopidogrel resistance, and these effects were marked in STEMI patients. In ROC curve analysis

of STEMI patients, TAFI level ≥136 iu/dL measured had a 78% sensitivity and 95% specificity,

vWF:Ag level ≥122.5 iu/dL measured had a 65% sensitivity and 95% specificity in predicting

clopidogrel resistance.

Conclusions: ACE D/D polymorphism and higher plasma levels of vWF:Ag and TAFI were

associated with clopidogrel resistance in ACS patients undergoing PCI, thereby adding evidences

for possible relationships. Therefore ACE D/D polymorphism, TAFI and vWF:Ag levels may be

useful markers in predicting loading dose of clopidogrel resistance after PCI in ACS, particularly

in STEMI patients. These findings could draw attentions to aspects of explaining antiplatelet

resistance other than drug metabolism, especially in era of newer antiplatelet agents.

Acknowledgements: The study (AR-2011/56) was supported by research grant from Gulhane

Military Medical Faculty Research Center.

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210

PLASMA PHENYLALANINE / TYROSINE RATIO AS PREDICTOR OF QUERCETIN

EFFECT ON LEFT VENTRICULAR REMODELING AFTER STEMI O.B. Iaremenko1, N.K. Iordanova1, P.F. Dudka1, T.M. Kuchmerovska2

1. Bogomolets National Medical University, Kyiv, Ukraine

2. Palladin Institute of Biochemistry of National Academy of Science, Kyiv, Ukraine

Background: The endothelial NO-synthase (eNOS) is one of the most important cardioprotective

signaling pathways. Cardioprotector quercetin (Qn) modulates eNOS activity, which also depends

on the bioavailability of tetrahydrobiopterin (4HB). In recent studies the increase in plasma

phenylalanine/tyrosine ratio (plPhe/Tyr) was considered as a marker of 4HB deficiency.

Objective: to evaluate the baseline plPhe/Tyr for prognosis of Qn effectiveness on the left

ventricular remodeling (LVR) in patients (pts) with ST-elevation myocardial infarction (STEMI).

Methods: We examined 36 pts with STEMI, who received treatment according to clinical

guidelines and additionally soluble Qn intravenously for five days. In all the pts the

echocardiography (EchoCG) on the first and tenth days and analysis of baseline plasma Phe and

Tyr levels by cation-exchanged liquid-column chromatography were performed. The outcome

effect was measured as minimal difference between baseline wall motion score index (WMSI) and

WMSI on the tenth day by amount 1/16 or 0.0625 (where 16 is a total number of LV segments).

Thus, the decrease of WMSI by ≥ 0.0625 was a criterion of positive LVR.

Results: The plPhe/Tyr in pts without positive LVR (2.41±0.74, n=14) was increased by 67.4% vs

healthy control (1.44±0.59, n=15, p<0.01) and by 41.8% vs pts with positive LVR (1.70±0.77,

n=22, p<0.05). The plPhe/Tyr was an independent predictor (by multiple logistic regression after

adjustment for all demographic, anamnestic, clinical and EchoCG data) of positive LVR (OR 0.30,

95%CI 0.10-0.88, p<0.05) with an area under ROC curve 0.75 (95%CI 0.57-0.88, p=0.006). The

sensitivity and specificity of plPhe/Tyr ≤ 2.06 (95%CI 1.29-2.06) were 81.8% and 71.4%

respectively.

Conclusion: An absence of increase in baseline plPhe/Tyr is an independent predictor of positive

LVR in early period after STEMI treated with Qn.

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211

OUTCOMES OF BIVALIRUDIN VERSUS HEPARIN ALONE IN PERCUTEANEOUS

CORONARY INTERVENTION H.I. Chaudry, B.W. Andrus, D. Bhatt, J.T. DeVries

Dartmouth Hitchcock Medical Center, Lebanon, NH, USA

Objective: To compare the real-world efficacy and safety of bivalirudin versus heparin in patients

undergoing percutaneous coronary intervention.

Background: Clinical trials have suggested that bivalirudin is as effective as heparin with lower

rates of bleeding. However, more recent studies have questioned these outcomes, especially when

heparin is used without adjuvant IIb/IIIa inhibitors.

Methods: We analyzed 8442 consecutive coronary interventions during a 10 year period ending

December 2012. Patients who received IIb/IIIa inhibitors were excluded. Multivariable logistic

regression was performed to correct for baseline differences.

Results: Bivalirudin was used in 5319 cases and heparin in 3123. When adjusted for all covariates,

there were no differences in the rates of procedural success or acute closure. However, bivalirudin

was associated with a lower incidence of severe post procedural complications including death

(OR 0.45 [0.30-0.68]), vascular complications (OR 0.68 [0.48-0.95]), retroperitoneal bleeding (OR

0.11 [0.03-0.38]) and transfusions (OR 0.44 [0.34-0.56]).

Conclusion: For patients undergoing PCI, bivalirudin provides similar efficacy and reduced risk

compared with heparin alone.

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212

TREATMENT DETERMINANTS OF NON CULPRIT VESSELS IN NOT

COMPLICATED ACUTE MYOCARDIAL INFARCTION: SINGLE SESSION VS

DEFERRED J.M. Telayna, J.M.H. Telayna, R.A. Costantini

Hospital Universitario Austral, Pilar, Argentina

Introduction: Among 20 - 60% of patients treated with primary coronary angioplasty (PTCA) have

multiple vessels disease (MVD), this being a predictor of mortality. The strategy of complete

revascularization (CR) in the same session is questioned.

Objective: To analyze clinical and angiographic variables of treatment decision and clinical

outcomes of early deferred CR (during the same hospitalization or within 30 days) vs. the index

procedure.

Method: Population: From May 2000 to December 2014, 374 patients with AMI were

consecutively treated, 189 of whom had MVD. In this period, 58 pts (group A) had CR in the same

session, while 35 pts (group B) completed deferred revascularization. Baseline characteristics:

mean age 58±11 vs 57±9 years, diabetes 15(29%) vs 7(20%); previous infarction 6(10) vs 6(17);

Killip Kimball C - D 9(15) v 1(3) p=0.08; IIbIIIa using 3(5) vs 9(26) p=0.008; time door to balloon

110±60 vs 107±59 minutes; anterior descending artery not related to infarction 21(36) vs 1(3)

p=0.0001; initial TIMI 0 32(55) vs 21(60); DES 10(17) vs 6(17); fluoroscopy time 19.2±15 vs.

16.9±13 minutes; dye 267.3±91 vs 236 milliliters.

Results: In-hospital: final TIMI III flow 58(100) vs 31(88) p=0.03, blush TIMI 3 final 52(90) vs

30(85) p=0.8; cardiac death 2(3) vs 0 p=0.5; reinfarction 1(2) vs 0 p=0.7. At follow-up 18±21.8 vs

23.9±18 months cardiovascular death 0 vs 1 (3) p=0.3; reinfarction 2 (4) vs 2(6) p=0.6, rePCI “de

novo” lesions 3(7) vs 2(6) p=1 and restenosis rePCI 2(4) vs. 3(8) p=0.3.

Conclusion: CR in AMI in the same session showed not higher risk or higher reintervention rate

against deferred modality in patients with MVD. The class > B in Killip Kimball; anterior

descending artery unrelated to the infarction support the decision for CR in the same session. The

chronic total occlusion and use of IIbIIIa made differ the CR.

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213

MAGNITUDE AND DECADE LONG TRENDS (2001-2011) IN PRE-HOSPITAL DELAY

IN ELDERLY PATIENTS HOSPITALIZED WITH ACUTE MYOCARDIAL

INFARCTION (AMI): INSIGHTS FROM THE WORCESTER HEART ATTACK

STUDY R. Makam, J. Gore, D. McManus, J. Yarzebski, R. Goldberg

University of Massachusetts Medical School, USA

Background: Early and aggressive intervention with medical and/or revascularization

interventions remains the cornerstone of AMI management. However, several high risk groups,

especially the elderly, are known to delay seeking medical care after the onset of AMI symptoms.

Current trends and factors associated with prolonged pre-hospital delay among older patients

presenting with AMI, particularly in different age strata within the elderly, are presently unknown.

Methods: Data from the Worcester Heart Attack Study, an ongoing population- based study of

residents of central MA hospitalized at all 11 medical centers in central MA with AMI on a

biennial basis between 2001 and 2011 were used.

Results: The mean duration of pre-hospital delay was 3.7 hours in patients 65 years and older. The

average delays were 3.9 hours, 3.9 hours, and 3.0 hours among those 65-74, 75-84, and 85 years

and older, respectively. While there was some suggestion of a slight decline in the average duration

of pre-hospital delay in the total study population (mean =4.0 hours 2001/2003; 3.2 hours

2009/2011), these encouraging declines were not consistently observed in each of the elderly age

strata examined. A variety of socio-demographic, medical history and clinical factors are being

evaluated in relation to prolonged pre-hospital delay in this patient population.

Conclusions: Prolonged care seeking behavior remains a continuing problem in elderly patients

hospitalized with AMI, though some recent improvements in care seeking behavior may be taking

place. Data will be presented on the characteristics of patients who exhibit prolonged, as compared

to those with shorter delay in the setting of AMI.

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DIABETES MELLITUS, OBESITY, THE METABOLIC SYNDROME AND ATHEROSCLEROSIS: BASIC AND CLINICAL

214

IMPACT OF DIABETES MELLITUS ON ACUTE HEART FAILURE

H.Y. Lee

Seoul National University Hospital, Seoul, South Korea

Background and aim: The prevalence of heart failure among diabetic patients is reported as 20%.

Conversely, several heart failure registry data reported high prevalence of diabetes mellitus

reaching 40%. Although, the outcomes in heart failure patients combined with diabetes mellitus

(DM-HF) have been suggested worse than those without diabetes (non-DM-HF), the effect of

glycemic control has not been reported yet.

Methods: We analyzed data from the Korean Acute Heart Failure (KorAHF) which is a registry of

patients hospitalized for acute heart failure syndrome in ten regionally-representative tertiary

university hospitals in Korea.

Results: 1) Among KorAHF registry patients, 40.0% had diabetes mellitus. DM-HF patients

were older (70.1¡¾11.6 vs 67.4¡¾16.0, p < 0.001), more men (55% vs 52%, p = 0.017), had more

hypertension (72% vs 50%, p < 0.001), chronic renal disease (21.6% vs 9.5%, p < 0.001), whereas

had less atial fibrillation (25.2% vs 29.1%, p =0.001) than non-DM-HF.

2) Ischemia was both the leading cause (52.7%) and the most frequent aggravating factor

(36.1%) in DM-HF patients, which were far more than in non-DM-HF patients (27.5% and 19.8%

respectively).

3) In-hospital mortality among DM-HF patients was 60% higher than non-DM-HF patients

(6.1% vs 3.9%, p < 0.001). The difference remained significant after adjusting gender, age, history

of hypertension, ischemic heart disease, functional status and serum creatinine.

Conclusions: DM-HF patients had worse prognosis than non-DM-HF patients. Hyperglycemic

control status might have little impact either on in-hospital mortality or short-term follow up.

Although DM-HF-OHA patients did not have worse outcome than non-DM-HF patients, DM-HF-

Insulin patients have three folds higher in-hospital mortality, which warrants long-term study.

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215

OBESITY AND LIPID INDEXES IN PATIENTS SUFFERING A FIRST ACUTE

CORONARY SYNDROME A.L. Arrebola-Moreno1, J.P. Arrebola1, D. Petrova2, R. Garcia-Retamero2,3,

A. Catena2, J.A. Ramirez-Hernandez1

1. Virgen de las Nieves University Hospital, Granada, Spain

2. Experimental Psychology Department, University of Granada, Spain

3. Center for Adaptive Behavior and Cognition, Max Plank Institute for Human Development,

Germany

Background and objectives: Obesity has reached epidemic proportions both in adults and children

in recent years and has been suggested to have adverse cardiovascular effects. The plasma

concentration ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) can identify

cardiometabolic risk and cardiovascular disease. Low-density lipoprotein cholesterol (LDL-C) and

non-HDL cholesterol have also been related to adverse CV prognosis and the ratio of total

cholesterol (TC) and HDL-C has been associated with carotid intima-media thickness. However,

to the best of our knowledge the capability of the different Obesity indexes to predict these lipid

indexes has not been systematically and specifically assessed in patients suffering a first acute

coronary syndrome (ACS).

Methods: We conducted a study including 98 consecutive patients suffering a first ACS. Patients´

height, waist, hip and weight were specifically measured in hospital, fasting, at 7 a.m. and three

days after the coronary event, using calibrated devices. Standardized questionnaires were used to

determine participants’ past medical history, medication, and cardiovascular risk factors. Fasting

venous samples were collected in all patients for the assessment of total cholesterol, HDL-C

cholesterol, low-density lipoprotein (LDL), cholesterol, and TG levels, which were all assessed

using standard enzymatic methods.

Result: Correlation analyses showed a significant association between patients weight, Body mass

index and waist-hip ratio, and both TG/HDL (r=0.21,p=0.04;r=0.25, =0.01; r=0.21,p=0.04,

respectively) and TC/HDL(r=0.22,p=0,03; r=0.31,p=0.003; r=0.21,p=0.04). No significant

association was found between the obesity indexes and LDL cholesterol and Non cholesterol.

Conclusions: Our results suggest that in patients suffering a first acute coronary event weight, BMI

and waist hip-ratio are good predictors of TG/HDL-C and TC/TG indexes. However, none of these

obesity indexes were associated with LDL-C and non-HDL-C. Probably, the main influence of

obesity in the lipid profile relies on TG and HDL-C but not in other cholesterol fractions.

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216

TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION REDUCES

METABOLIC DISTURBANCES INDUCED BY HIGH-FRUCTOSE DIET IN RATS V.K. Spiridonov, Z.S. Tolochko, T.A. Korolenko

Institute of Physiology, Novosibirsk, Russia

Background: Metabolic syndrome (MS) precedes the development of insulin-independent

diabetes. The sensory nerves (SN) are involved into the regulation of carbohydrate and lipid

metabolism. Moreover, the obesity and diabetes often resulted in sensory neuropathy.

Objective: The purpose of present study is to investigate the effects of SN low-frequency

transcutaneous electrical stimulation (TES) on the development of MS induced by high-fructose

diet in rats.

Methods: Male Wistar rats received 12,5 % fructose solution in their drinking water for 10 weeks.

Control rats were given tap water to drink. 8 weeks after drinking fructose or tàp water rats were

subjected to TES (1mA, 2 Hz, pulse duration 0,5 msec, 10 min, daily for 2 weeks) applied to

the paws. The blood contents of triglyceride (TG), products of lipid peroxidation (PLP) and

glucose in intraperitoneal glucose tolerance test were quantified spectrophometrically.

Results: The consumption of fructose resulted hypertriglyceridemia, oxidative stress, impaired

glucose tolerance. TES applied to rats with fructose diet induced the decrease in content of TG

and products of PLP versus control values and improved glucose tolerance test ( P< 0,05 ). TES

had no effect on these parameters in control rats. There was no difference in the fasting glucose

concentration between all groups.

Conclusion: We can conclude that TES reduces the MS-induced disturbances and decreased the

risk of insulin-independent diabetes development.

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217

INDIVIDUAL FACTORS, LIFE EVENTS AND GENETIC VARIABILITY

ASSOCIATED WITH OBESITY, MEDELLIN, COLOMBIA

A.V. Valencia, B.R. Escobar, C. Gardner, C.A. Agudelo, L.M. Martínez, J.S. Lopera,

S. Rojas, L. Jaramillo, M. Zapata, I. Ortiz

Universidad Pontificia Bolivariana, Sede Central Medellín, Colombia

Objective: Relate to individual factors, life events and genetic variability associated with obesity.

Background: Obesity is a complex and multifactorial, chronic disease which is the result of the

interaction between genetic factors, behavioral and environmental.

Methods: Study of quantitative, analytical, type descriptive-correlational study scope. We included

people between 18 and 30 years with a diagnosis of obesity in which the following instruments

were used: YSQ-L2 (early wrong adaptive schema), NEO PI-R (personality), USQ (vital events);

in addition the genotyping for polymorphisms rs1501259 of the ADIPOQ gene, rs6265 of the

BDNF gene and rs9939609 the gene FTO.

Results: We included 74 patients, with an average age of 40.3 years; the 88.1 per cent were women,

and the average body mass index was 38 Kg/m2. With respect to the genotyping, the found

frequencies were as follows: 0.25 and 0.74 for the alleles A and C of the ADIPOQ gene rs1501299

polymorphism, respectively; 0.20 and 0.79 for the T and C polymorphism of BDNF gene rs6265

alleles, respectively; and 0.35 and 0.64 for alleles A and T of the gene FTO rs9939609

polymorphism, respectively.

Conclusions: The minimum allelic frequency identified for the T allele of the rs6265 is expected

for a not synonymous polymorphism with involvement on the function of the protein. The

frequencies of allele found in this study are similar to those reported for the European population.

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218

RELATIONSHIP BETWEEN ADMISSION FREE TESTOSTERONE LEVEL AND

INSULIN-RESISTANCE IN ACUTE MYOCARDIAL INFARCTION T. Nunohiro1, M. Kurobe1, K. Minami1, S. Furudono1, Y. Uchida1, S. Takeshita1,

H. Nakashima1, K. Maemura2

1. Nagasaki Harbor Medical Center City Hospital, Nagasaki, Japan

2. Nagasaki University, Nagasaki, Japan

Background: Previous studies in elderly men have shown an association between low levels of

testosterone and higher risk for Cardio Vascular Disease; however, prospective studies in younger

men lacking. Sweden researchers reported a strong and independent association between

concentrations of testosterone and AMI was observed in men with type 2 diabetes. (2013 ESAD:

European Association for the Study of Diabetes).

Objective: The aim of this study is to examine the association between free testosterone (fT ) and

insulin-resistance in AMI. Testosterone impact of insulin-resistance remains unclear.

Methods and Results: This study included of 126 subjects who underwent primary percutaneous

coronary intervention. Patients were divided 3 groups according to 75g OGTT. Diabetes mellitus

group were 45 and IGT group were 34 and normal glucose tolerance were 47.And patients divided

into two groups according to median fT level(7.8pg/ml).We investigated a low plasma free

testosterone level is related to atherosclerosis in men with coronary risk factor. Patients we

underwent measurement of CAVI, AI, RHI (endothelial function) and insulin-resistance were

enrolled. The relation between low fT and CAVI, AI, RHI and insulin-resistance were analyzed.

Low fT patients were significantly 45 and correlated with Admission insulin (R=-

0.41,p=0.01),HOMA-IR(R=-0.30,p=0.04), while HOMA-Iβ(R=-0.02,p=0.88)was not. FT is a

trend of an inverse association between serum testosterone and fasting insulin (R=-

0.28,p=0.06).Low fT patients with DM showed high CAVI compared to high fT patients (P=0.04),

not high AI nor low RHI. Low fT patients with IGT and normal glucose tolerance did not high

CAVI.

Conclusion: We think low testosterone with diabetes patients where early vascular aging is

observed and suggest that low testosterone is associated insulin-resistance.

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219

BEST PREDICTOR OF METABOLIC SYNDROME: COMPARISON OF VARIOUS

ANTHROPOMETRIC AND ATHEROGENIC PARAMETERS IN THE KAZAKH

POPULATION IN XINJIANG PROVINCE C.H. He1,2,3, Y. Chen1,2, Y.T. Ma1,2, Y.N. Yang1,2, X. Ma1,2, X.M. Li1,2, Z.Y. Fu1,2,

X. Xie1,2, Z.X. Yu1,2, F. Liu1,2

1. The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China

2. Xinjiang Key Laboratory of Cardiovascular Disease Research, Urumqi, Xinjiang, China

3. Cardiovascular Research Foundation, New York, NY, USA

Aims: Few studies have investigated the metabolic syndrome (MetS) in the Kazakh population in

China. This study aimed to evaluate the best single predictor of the MetS by comparing various

anthropometric and atherogenic parameters in adult Kazakhs.

Methods: 4094 Kazakhs were recruited from the Cardiovascular Risk Survey which was carried

out from 2007 to 2010. Anthropometric data, blood pressure, serum total cholesterol, triglyceride,

low density lipoprotein cholesterol, high density lipoprotein cholesterol and fasting plasma glucose

were documented. MetS and its components were confirmed according to IDF criteria. Areas under

the curve (AUCs) of each variable for the presence of MetS were compared. The sensitivity (Sen),

specificity (Spe), shortest distance in the receiver’s operating characteristic curve (ROC) and

cutoffs of each variable to diagnose MetS were calculated.

Results: 28.6% of men and 31.0% of women had MetS in the Kazakh population. In men, WHtR

had the highest AUC value 0.821, followed by BMI (0.801), TG/HDL-C (0.792), WHR (0.776)

and BAI (0.666). In women, WHtR also had the highest AUC value (0.835), following by BMI

(0.789), WHR (0.778), TG/HDL-C (0.778) and BAI (0.751). Similarly, among all 5

anthropometric and atherogenic parameters, WHtR had the shortest ROC distance of 0.37

(Sen=81.09%, Spe=68.50%); the optimal cutoff for WHtR was 0.55 in men. In women, WHtR

also had the shortest ROC distance of 0.35 (Sen=84.59%, Spe=68.97%); the optimal cutoff of

WHtR was 0.54.

Conclusion: WHtR was the best predictor of MetS in both Kazakh men and women.

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LEFT VENTRICULAR HYPERTROPHY / HYPERTROPHIC CARDIOMYOPATHY / DIASTOLIC DYSFUNCTION

220

YAMAGUCHI SYNDROME: A POTENTIALLY UNDER-RECOGNIZED ENTITY?

T.T Choksi, S. Sapkota, A. Salei, E. Mizrahi

Mercy Catholic Medical Center, Philadelphia, PA, USA (an affiliate of Drexel University

College of Medicine)

Background: Yamaguchi syndrome, also known as apical variant hypertrophic cardiomyopathy

(HCM), as per most studies, accounts for only 1-2% of all HCM cases in non-Japanese population.

We report a cases series of this rare HCM variant in African-American patients suggesting the

possible under-recognition in this population.

Cases: (1) A 57 year old Afro-American male who was hospitalized for distal radius fracture,

reported transient dizziness. Electrocardiogram (EKG) showed left ventricular hypertrophy (LVH)

with giant T wave inversions in antero-septal leads. Trans-thoracic echocardiogram (TTE) showed

abnormal apical hypertrophy without mid-cavitary gradient. Cardiac MRI (CMR) was obtained

confirming apical-variant HCM. He was later discharged on Metoprolol. (2) A 53 year old Afro-

American female presented following a syncopal episode. She reported intermittent dizziness for

last 2 months. EKG showed LVH and deep T wave inversion in pre-cordial leads. TTE showed

severe apical hypertrophy. CMR confirmed the Yamaguchi syndrome. Pt had recurrent non-

sustained ventricular tachycardia during hospitalization. She underwent implantable defibrillator

placement and was discharged on Diltiazem.

Discussion: Apical HCM is characterized by hypertrophy of the myocardium predominantly in the

apical region of the left ventricle (LV). Most patients have a relatively benign course, but

occasionally significant arrhythmias, sudden cardiac death and apical infarctions with apical

aneurysms can occur. Typical features include "giant" T wave negativity on the EKG, particularly

in the precordial leads and a “spade-like configuration” of the LV cavity at end-diastole on left

ventriculography.

Echocardiography has its limitations in evaluating the apex. CMR is the preferred modality for

diagnosis, as it not only helps identify functional and morphological abnormalities of the apex but

can aid in detection of apical myocardial injury.

Given these cases of apical HCM presented in a short time-span, it raises the question whether it

is potentially under-recognized in the Afro-American population!

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LEFT VENTRICULAR HYPERTROPHY / HYPERTROPHIC CARDIOMYOPATHY / DIASTOLIC DYSFUNCTION

221

TRANSTHYRETIN AMYLOID CARDIOMYOPATHY TREATMENT WITH AN

ANTISENSE OLIGONUCLEOTIDE INHIBITOR OF TTR (ISIS-TTR RX) M.D. Benson1, E.J. Ackermann2, B. Monia2

1. Indiana University School of Medicine, Indianapolis, IN, USA

2. ISIS Pharmaceuticals, Inc., Carlsbad, CA, USA

Introduction: Transthyretin (TTR)-mediated amyloidosis (ATTR) is a systemic protein deposition

disease characterized by peripheral neuropathy and restrictive cardiomyopathy. In prior studies

we have shown that progression of cardiac amyloidosis can be documented over a 12 month period

by measuring left ventricular mass (LVM) by both echocardiography and magnetic resonance

imaging (MRI). We have now initiated a single center, investigator sponsored, open-label clinical

study to assess the safety and tolerability and as a secondary objective to determine if disease

progression can be attenuated by suppressing the hepatic synthesis of TTR by treatment with ISIS-

TTR Rx, a 2nd-generation 2'-MOE chimeric ASO specific for the TTR mRNA. Previous studies

have demonstrated ISIS-TTR Rx produced 95% reductions in serum TTR levels in a transgenic

mouse model.

Methods: Subjects are admitted to study with biopsy-proven ATTR and LV wall thickness of ≥1.3

cm. Baseline studies include echocardiography and cardiac MRI. Echocardiography is conducted

at 12 and 24 months. MRI is conducted at 24 months. Serum TTR levels and safety measures are

monitored at regular intervals throughout the 24 month treatment period. ISIS-TTR Rx 300 mg is

administered weekly by subcutaneous injection.

Results: Five patients have been admitted to the study. To date, three of the patients have been

treated >4 months and two patients >1 month. ISIS-TTR Rx appears to be well tolerated.

Conclusion: ISIS-TTR Rx appears to be well tolerated in patients with ATTR cardiomyopathy.

Efficacy evaluation awaits longitudinal studies aimed at determining stability of left ventricular

mass.

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CARDIOMYOPATHIES: PATHOGENESIS AND TREATMENT

222

GENETICS AND GENOTYPE-PHENOTYPE CORRELATIONS IN FINNISH

PATIENTS WITH DILATED CARDIOMYOPATHY O. Akinrinade1,2, L. Ollila3, S. Vattulainen1, J. Tallila4, M. Gentile4, H. Koillinen5,

S. Myllykangas2,4, T.P. Alastalo1,4, J.W. Koskenvuo4,6,7, T. Helio3

1. Hospital for Children and Adolescents, Institute of Clinical Medicine, University of Helsinki,

Finland

2. Institute of Biomedicine, University of Helsinki, Finland

3. Department of Cardiology, University Hospital Helsinki, Finland

4. Blueprint Genetics, Helsinki, Finland

5. Department of Genetics, University Hospital Helsinki, Finland

6. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku,

Finland

7. Department of Clinical Physiology and Nuclear Medicine, HUS Medical Imaging Center,

Helsinki University Central Hospital and University of Helsinki, Finland

Background: Despite our increased understanding of the genetic basis of dilated cardiomyopathy

(DCM), the clinical utility and yield of clinically meaningful findings of comprehensive next-

generation sequencing (NGS) based genetic diagnostics in DCM has been poorly described. We

utilized a high quality oligonucleotide-selective sequencing (OS-Seq) based targeted sequencing

panel to investigate the genetic landscape of DCM in Finnish population and evaluate the utility

of OS-Seq technology as a novel comprehensive diagnostic tool.

Methods and results: Using OS-Seq, we targeted and sequenced the coding regions and splice

junctions of 101 genes associated with cardiomyopathies in 145 unrelated Finnish patients with

DCM. We developed effective bioinformatic variant filtering strategy and implemented strict

variant classification scheme to reveal diagnostic yield and genotype-phenotype correlations.

Implemented OS-Seq technology provided high coverage of the target region (median coverage

410x and 99.42% of the nucleotides were sequenced at least 15x read depth). Diagnostic yield was

34.5% (familial 47.6% and sporadic 24.4%, p=0.004) when both pathogenic and likely pathogenic

variants are considered as disease causing. Of these, 20 (53%) were TTN truncations (nonsense

and frameshift) affecting all TTN transcripts in 20 cases. TTN truncations accounted for 20.6%

and 14.6% of the familial and sporadic DCM cases, respectively.

Conclusion: Panel-based high-quality NGS enables high diagnostic yield especially in familial

form of DCM and bioinformatic variant filtering is a reliable step in the process of interpretation

of genomic data in a clinical setting.

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223

THE CARDIOPROTECTIVE EFFECTS OF GRANULOCYTE-COLONY

STIMULATING FACTOR (GCSF) IN PATIENTS RECEIVING ANTHRACYCLINE

CHEMOTHERAPY S. Lahsaei1, D. Le2, S. Rahmani3, H. Ren3, D. Irwin3

1. California Pacific Medical Center, San Francisco, CA, USA

2. St Mary's Medical Center, San Francisco, CA, USA

3. Alameda County Medical Center, Oakland, CA, USA

Background: Anthracycline cardiotoxicity is an adverse effect in patients treated for malignancies.

In clinical practice, GCSF is used in adjunct to myelosuppressive chemotherapy. There has been

benefit with GCSF in post myocardial infarction patients by modulating the regeneration of

myocardial tissue. However, the cardioprotective role of GCSF in patients with anthracycline

cardiotoxicity has not been well studied. In this study we evaluated GCSF and its effect on systolic

function in patients receiving anthracycline chemotherapy.

Methods: From January 2006 to December 2010, a retrospective cohort study was done to identify

all patients who received anthracycline chemotherapy treated either with or without GCSF and had

at least 2 transthoracic echocardiograms. The primary measure was the change in left ventricular

ejection fraction measured before and after anthracycline chemotherapy in patients who received

GCSF compared to patients who did not receive GCSF. Simpson’s technique was used to evaluate

the change in LVEF while t-test and regression analysis were used to compare differences between

both groups.

Results: Seventy-nine patients were identified. Overall there was a decrease in mean LVEF

between patient who did not received GCSF (baseline LVEF M=61.9% vs. post treatment LVEF

M=59.0%, CI95%, p=0.026) compared to those who received GCSF (baseline LVEF M=61.7%

vs. post treatment LVEF M=59.2%, CI95%, p=0.033). There was a greater decrease in mean LVEF

in the non GCSF group (2.9%) compared to the GCSF group (2.5%). When adjusted for age,

gender, use of beta-adrenergic antagonists, ACE inhibitors, and adjunctive cardiotoxic drugs, there

was no significant difference between both groups (beta: 0.26; p=0.890).

Conclusion: The present study suggests that GCSF preserves systolic function in patients receiving

anthracycline chemotherapy. Further prospective studies are needed to better discern the

relationship between GCSF and its cardioprotective role and other echocardiogram parameter in

patients who receive anthracycline chemotherapy.

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224

HOSPITAL ADMISSIONS IN A HIGH RISK HEART FAILURE POPULATION

MANAGED WITH A TEAM BASED APPROACH IN A LARGE URBAN

HEALTHCARE DELIVERY MODEL I. Kedan, R. Khandwalla, K. Birkeland

Cedars Sinai Hospital, Beverly Hills, CA, USA

Background: Hospital admissions drive heart failure (HF) costs. Team based management

improves outcomes.

Purpose: Demonstrate the impact of a team based program at Cedars Sinai Healthcare Foundation

on hospital admissions and readmissions.

Methods: High risk patients were identified from an outpatient panel of 3,500 patients. The HF

program includes cardiologists, a clinical pharmacist, nutritionist, home nurse practitioners, and

palliative care. Services offered included education, medication reconciliation and optimization

based on clinical parameters, serum brain natriuretic peptide, and point of care ultrasound IVC

measurements. Retrospective review of over 28 months (11/2012-2/2015) was conducted. Cedars

Sinai Hospital and Olympia Medical Center hospital admissions were included.

Results: 6 months Of 213 patients, 34 were excluded (HF resolved/discharged 4; Declined follow-

up 11; Transfer of care 8; Lost to follow-up 2; Hospice 4; Deceased 5). 179 patients (84%)

participated for 6 months. There were 148 hospital admissions (0.8/patient) and 32 30-day

readmissions (0.18/patient) 6 months pre-enrollment. There were 81 hospital admissions

(0.46/patient) and 23 30-day readmissions (0.13/patient) 6 months post-enrollment. These

findings resulted in a 45.3% reduction in hospital admissions (p 0.00004) and a 28.1% reduction

in 30-day readmissions (p 0.4).12 months Of 163 patients, 50 were excluded (HF

resolved/discharged 8; Declined follow-up 11; Transfer of care 9; Lost to follow-up 4; Hospice

10; Deceased 8). 113 patients (69.3%) participated for 12 months. There were 114 admissions

(0.1/patient) and 23 30-day readmissions (0.2/patient) 12 months pre-enrollment. There were 65

admissions (0.6/patient) and 12 30-day readmissions (0.1/patient) 12 months post-enrollment.

These findings resulted in a 43.0% reduction in hospital admissions (p 0.0002) and a 47.8%

reduction in 30-day readmissions (p 0.05).

Conclusions: The HF program demonstrated reduced hospital admissions at 6 and 12 months. 30-

day readmissions decreased at 12 months.

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225

ECHOCARDIOGRAPHIC PROFILE AND IMMUNOLOGIC FUNCTION IN HIV-

INFECTED PATIENTS V.B. Salvador, C. Ezenwa, F. Radparvar

Icahn School of Medicine at Mt. Sinai/Queens Hospital Center, Jamaica, NY, USA

Echocardiographic abnormalities are commonly identified in HIV-infected individuals even while

on treatment with highly active antiretroviral therapy. The present case series was meant to provide

a descriptive profile of the putative correlation between the type and severity of echocardiographic

cardiac abnormalities and the immunologic status in terms of CD4 count and HIV viral load. The

study was designed as a retrospective cross-sectional cohort of adult patients infected with HIV on

treatment with antiretroviral agents, seen in the outpatient Cardiology clinic between January 2007

and January 2013. Electronic medical records were reviewed for eligible patients whose

cardiomyopathy was from no other source other than HIV infection which was serologically

confirmed. Of the twenty patients screened consecutively, nine patients with relatively preserved

immunologic status and low viral load were found to have varying degrees of echocardiographic

abnormalities including pulmonary hypertension, systolic dysfunction, severe valvular

regurgitation, pericardial effusion, and diastolic dysfunction. There was no discernible trend

between the degree of echocardiographic abnormalities and the extent of immunologic

dysfunction. The relatively preserved CD4 count of more than 200/mL and substantially low viral

load of less than 100,000 copies/mL did not appear to predict the degree of systolic dysfunction

and pulmonary hypertension while on HAART regimen. The echocardiographic abnormalities

could not be attributed solely to HIV infection, level of viral load and CD4 count. Other factors

might potentially contribute to the development of cardiac abnormalities among HIV-infected

individuals while on treatment.

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226

PHARMACIST INVOLVEMENT TO IMPROVE CARE OF HEART FAILURE

PATIENTS AS THEY TRANSITION FROM HOSPITAL TO HOME

M.I. Achi

Houston Methodist Houston, Houston, TX, USA

Background: Better Outcomes by optimizing Safe Transition (also known as BOOST) is a

project/program aimed at improving care of patients as they transition from hospital to home. It

provides evidence-based clinical interventions that can be easily adapted and integrated into each

unique hospital environment. The goal for pharmacy was to identify/intervene on heart failure

medication related issues in moderate to high risk patients, which included: side effects, drug

interactions, polypharmacy, education, cost, family involvement, and efficient collaboration with

other providers and disciplines. The primary purpose of this study is to increase pharmacist patient

encounter at discharge and thereby increase hospital consumer assessment of healthcare providers

and systems (HCAPS) score for patient understanding of heart failure medications.

Method: High risk heart failure patients were simply identified as patients with >5 medications

and/or with diagnosis for heart failure. Pharmacist was consulted upon admission to reconcile

home medications and other medication related issues, such as cost, side effects, polypharmacy,

compliance etc. Upon discharge pharmacist was consulted to give a comprehensive verbal and

written (calendar) medication education. HCAPS scores were reported monthly through patient

survey.

Results: In 2012 pharmacist discharge counselling/support for one heart failure floor was

approximately 200 encounters, 2013 it was approximately 700 encounters, by 2014 it increased to

approximately 900 encounters. There was a 77% increase in pharmacist involvement for safe

medication discharge. This translated to 73% HCAPS score for patient’s positive “understanding

of what medicine is for” from 55 % prior to BOOST project.

Conclusion: Pharmacist involvement in heart failure patients at discharge and during

hospitalization was associated with increase in patient understanding of heart failure medications,

which translates to patient safety and better compliance.

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227

ANDROGENIC ANABOLIC STEROIDS INDUCED DILATED CARDIOMYOPATHY

PRESENTED WITH ISCHEMIC STROKE M.S. Salih, E. Leung, Y. Huang, C.K. Reiss

St Luke's hospital, Chesterfield, MO, USA

Backgrounds: Androgenic anabolic steroids (AAS) are often used by many athletes or

bodybuilders to increase muscle mass and to enhance performance. This comes with multiple side

effects, some of which can be life-threatening or irreversible. There have been a few case reports

that previously suggested an association between AAS use and dilated cardiomyopathies. We

report a case of a patient with chronic AAS use, who presented with an acute ischemic stroke and

severe dilated cardiomyopathy with systolic dysfunction.

Case: This is a 37 year old bodybuilder male with a past medical history of hyperlipidemia and

tobacco abuse who presented with an acute ischemic stroke. He had been self-administering

anabolic androgens for the past three years. He presented with left-sided weakness, slurred speech

and left facial droop. He had shortness of breath with activity and occasional palpatations for a

few weeks prior to the admission. An initial CT scan of the brain did not show any acute process.

He was given tPA upon arrival to the hospital. An echocardiogram showed global dilatation of the

heart with global hypokinesia of the left ventricle. An estimated ejection fraction was 20%. A

follow-up MRI of the brain showed hemorrhagic conversion of the infarction. A CT angiogram of

the coronary arteries was normal. The patient was treated and discharged with lisinopril,

metoprolol and spironolactone. A cardiac MRI two months later also showed severe left

ventricular enlargement and severe global hypokinesia without any areas of delayed contrast

enhancement.

Conclusions: This patient developed an ischemic stroke as a complication of dilated

cardiomyopathy which was possibly associated with the use of AAS. It is important for physicians

to be mindful of potential side effects associated with chronic AAS use. We have presented an

unusual and near lethal presentation of a potential condition induced by anabolic steroid use.

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228

STRUCTURED EATING PLAN IN PATIENTS WITH HEART FAILURE S.M. Kim, H. Silvet

Loma Linda VA Healthcare System, Loma Linda, CA, USA

Objective: To test the feasibility of 3-month structured eating plan (STEP), assess the effectiveness

of the intervention, and assess potential barriers to dietary behavior in veterans with heart failure

(HF).

Background: HF outcomes are related to patient compliance, adherence to lifestyle and diet, and

medication management. Adherence to dietary guidelines has been shown to be lower than

adherence to medications and is associated with increased admissions for HF. While proper

nutrition is recognized as an important part of HF management, the official dietary guidelines for

patients with HF are limited and somewhat vague and inconsistent. Methods: This is prospective

observational pilot study. Twenty-three veterans with HF were recruited in the intervention.

Patients’ dietary barriers were assessed using semi-structured questionnaires. Patient-centered,

individualized, and structured meal plan was formulated in collaboration with HF nurse

practitioner (NP) and dietitian talking into patients’ food preference, assess, availability, and

affordability.

Results: The percentage of patients who agreed to participate was 72%; the percentage of patients

who were recruited and completed the intervention was 52%; and the percentage of patients who

completed the food records and kept their intervention was 80%. Blood tests were measured pre

and post intervention. Serum creatinine level was significantly improved after intervention (P

<0.05).

Conclusions: The findings of this pilot study showed that a structured, patient-specific eating plan

for veterans with HF was feasible in the VA healthcare system.

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229

THE ROLE OF EPIDEMIOLOGICAL CORONARY ARTERY DISEASE RISK

FACTORS IN TAKO-TSUBO CARDIOMYOPATHY

S. Banga, A. Aggarwal, N. Wiegley, C. Shaw, T. Lynch, S. Mungee

University of Illinois College of Medicine at Peoria, IL, USA

Background: Tako-tsubo cardiomyopathy (TTC) is a syndrome that present with ST elevation/

depression on electrocardiogram, elevated cardiac enzymes and signature echocardiogram

findings. Severe physical and emotional stressors have been shown to precipitate this syndrome.

Objectives: We aim to study the incidence of both the modifiable and non-modifiable CAD risk

factors in patients presenting with TTC and STEMI at our tertiary care center.

Methods: Retrospective analysis of 429 patients who presented with ST elevation, raised cardiac

enzymes and wall motion defect between July 2012 to May 2014, was performed. They were

classified into TTC group without significant CAD and STEMI group with obstructive CAD on

coronary angiography. Different traditional modifiable and non-modifiable CAD risk factors were

compared between the two populations.

Statistical analysis was performed using SPSS 22 version (Armonk, NY: IBM Corp).

Results: Among all 429 patients, TTC group had 182 patients with mean age of 69±12.4 years

versus the STEMI group who had 247 patients with mean age of 61.2±13.1 years (<0.001).

The distribution of different CAD risk factors in TTC group versus STEMI group included female

gender with 90.2% versus 26% (p<0.001); family history of premature CAD in 27% versus 5.3%

(p<0.001); hypertension in 50% versus 66.8%( p<0.001); diabetes in 16.5% versus 24.7%

(p=0.05); dyslipidemia in 61 % versus 73.6% (<0.5); history of tobacco use in 32.4% versus

46.2%(p<0.05) respectively.

Anxiety and depression was the precipitating cause in 12.6 % (23) patients in the TTC group.

Conclusions: CAD risk factors have a good association with TTC as with STEMI. Female gender

and family h/o premature CAD had significant correlation with the TTC whereas hypertension,

diabetes and tobacco history had higher probability with STEMI. Our study suggests that there

may be a missing link with the risk factors promoting atherosclerosis in patients with Tako-tsubo

cardiomyopathy despite established neurogenic pathogenesis.

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NEW INSIGHTS INTO PATHOGENESIS AND MANAGEMENT OF HEART FAILURE

230

IMPACT OF THE BETA-1 ADRENERGIC RECEPTOR POLYMORPHISM ON

TOLERABILITY AND EFFICACY OF BISOPROLOL THERAPY IN HEART

FAILURE PATIENTS

H.Y. Lee

Seoul National University Hospital, South Korea

Background: The association between the coding region variations of adrenergic receptor genes

and the therapeutic effect were investigated in congestive heart failure (CHF) patients.

Methods and Results: 100 symptomatic CHF patients with LVEF < 45% were enrolled. Enrolled

patients started bisoprolol 1.25mg once daily, up-titrated to the maximally tolerable dose, and were

treated for 1 year. Genotypic analysis was carried out, but the results were double-blinded

throughout the study period. 1) At position 389 of the beta-1 adrenergic receptor, the observed

minor Gly allele frequency was 21% and no deviation from Hardy-Weinberg equilibrium was seen

in the genotypic distribution of Arg389Gly (p=0.75). 2) Heart rate was reduced from 80.814.3 to

70.015.0 BPM (p<0.0001). There was no significant difference in the final heart rate across the

genotypes. However, Arg389Arg genotype group required significantly larger amount of

bisoprolol compared with Gly389X (Gly389Arg+Gly389Gly) group (5.262.62 mg vs

3.962.05mg, p=0.022). 3) There were no significant differences in the changes of LVEF or

remodeling between two groups. There was no significant difference in exercise capacity or BNP

level change, either. 4) However, interestingly, there was two-fold higher rate of readmission

(21.2% vs 10.0%, p=0.162) and one HF-related death in Arg389Arg group. Conclusion: ABRB1

Gly389X genotype showed greater response to bisoprolol than Arg389Arg genotype, suggesting

the potential of individually tailoring of beta-blocker therapy according to genotypes.

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NEW INSIGHTS INTO PATHOGENESIS AND MANAGEMENT OF HEART FAILURE

231

A RARE CASE OF CARDIAC TAMPONADE INDUCED BY CHRONIC

RHEUMATOID ARTHRITIS T. Yousuf1, J. Kramer2, S. Sanyal3, J. Ziffra1



3. University of Illinois College of Medicine, Chicago, IL, USA

Background: Rheumatoid Arthritis (RA) is a chronic inflammatory autoimmune disease primarily

involving the joint synovium. The severity of the disease and symptom manifestations are variable

from patient to patient. RA is a systemic disease, which has many known extra-articular

manifestations.

Case: We present a unique case of a patient with long standing RA on adalimumab and

hydroxychloroquine who presented with a primary complaint of chest and back pain.

Echocardiography revealed borderline normal left ventricular function and a large pericardial

effusion with the finding of elevated intrapericardial pressure suspicious for cardiac tamponade.

Infectious workup including Human Immunodeficiency Virus, Ebstein Barr Virus,

Cytomegalovirus, Tuberculosis and Mycoplasma were all found to be negative. The presence and

elevation of anti-cyclic citrullinated peptide antibody, rheumatoid factor and C-reactive protein

confirmed that the patient was having an active flare up of his longstanding rheumatoid arthritis.

It was determined that this flare up was the cause of the cardiac tamponade. A pericardiocentesis

was performed and 850 cc of bloody fluid was drained. Additionally, colchicine was prescribed to

help reduce the pericardial thickening and prevent relapse. The patient remained stable and

asymptomatic following the pericardiocentesis and was discharged with instructions to follow up

with cardiology and rheumatology. At his follow up visit, repeat echocardiogram showed no signs

for pericardial effusion or thickening.

Conclusion: Although there has been extensive study of rheumatoid arthritis, there are only a few

documented cases noting the occurrence of cardiac tamponade in these patients. Therefore, it is

important for the clinician to be aware of and recognize this potentially serious cardiac outcome

associated with a common rheumatologic condition.

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LIPIDS, STATINS AND CVD

232

STATIN INTOLERANCE - MECHANISMS, RISK FACTORS, DEFINITION AND

MANAGEMENT

M. Banach

Department of Hypertension, Medical University of Lodz, Poland

Statins are one of the most commonly prescribed drugs in clinical practice. They are usually well

tolerated and effectively prevent cardiovascular disease (CVD) events. Most statin therapy-related

adverse effects are muscle-related, such as statin-induced myalgia or myopathy (SIM), as well as

muscle weakness and myosis. The recent consensus paper of the European Atherosclerosis Society

(EAS) has focused on statin-associated muscle symptoms (SAMS), and avoided the use of the

term 'statin intolerance'. Although muscle syndromes are the most common adverse effects

observed after statin therapy (even up to 29% according to the EAS statement), excluding other

side effects might underestimate the number of patients with statin intolerance, which might be

observed in 10 - 15% of patients. In case of these patients one should also always remember to

exclude other causes of statin intolerance, including so-called nocebo effect. In clinical practice,

statin intolerance limits effective treatment of patients at risk of, or with, CVD. Knowledge of the

most common adverse effects of statin therapy that might cause statin intolerance and the clear

definition of this phenomenon is crucial to effectively treat patients with lipid disorders. Therefore,

the recent position paper of International Expert Lipid Panel was prepared to suggest a unified

definition of statin intolerance, and to complement the recent EAS statement on SAMS, where the

pathophysiology, diagnosis and the management were comprehensively presented. Besides the

discussion around statin intolerance definition, the lecture will also discuss in details the most

important issues on the suitable statin intolerance management, especially in patients at high CV

risk.

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233

GENETICS OF TRIGLYCERIDE-RICH LIPOPROTEINS AND ATHEROSCLEROTIC

CARDIOVASCULAR DISEASE

R.S. Rosenson

Icahn School of Medicine at Mount Sinai, New York, NY, USA

Triglyceride-rich lipoproteins (TGRLs) comprise a vast array of intestinally-derived and

hepatically-secreted particles with distinct compositions and associations with risk for

atherosclerotic cardiovascular disease (ASCVD) or pancreatitis. Although the contribution of

plasma/serum triglycerides (triacylglycerols [TG]) to increased risk of ASCVD was established in

multivariate models that adjust for major risk markers, including LDL cholesterol and HDL

cholesterol. Despite the association of circulating TGRL levels with atherosclerosis, it has been

uncertain whether abnormal TGRL metabolism and/or TGRL lipolytic products are involved in

the causal pathway for ASCVD. Human genetic studies identified new proteins involved in TGRL

metabolism, revealed insights into the genetic architecture of plasma TG, and clarified the

contribution of TGRL to human CVD. The genetic architecture for TG in the population appears

to be a mosaic comprised of rare large-effect variants, common small-effect variants, and

environmental influences. Variants associated with common, complex traits like plasma TG range

from common (>1:20 frequency), to low frequency (1:200 to 1:20), to rare (<1:200). About 50%

of interindividual plasma TG variability is estimated to come from DNA sequence variants. A

comprehensive logistic regression model from GWAS that included clinical variables and both

common and rare genetic variants explained 42% of total variation in hypertriglyceridemia

diagnosis. Genetics can be used to distinguish causal from reactive processes in humans and such

studies suggested that plasma TG causally relates to CHD. Common, low frequency, and/or rare

DNA sequence variants in 4 TGRL metabolism genes that are functionally related to LPL have

been convincingly associated with CHD risk. Human genetic data suggest that therapeutic

strategies that enhance LPL function, decrease APOC3 function, decrease ANGPTL4 function, or

enhance APOA5 function are important targets for prevention of ASCVD.

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234

USE OF PCSK9 INHIBITORS IN STATIN INTOLERANT PATIENTS: ROLE FOR

THE FUTURE?

S.L. Kopecky

Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA

While the HMG-CoA reductase inhibitors have been lifesaving drugs for many millions of

patients, intolerance to these agents has estimated to be 5-10% of patients, and may approach 20%

in certain populations. The new PCSK9 inhibitors (Proprotein Convertase Subtilisin/Kexin Type

9) will soon be reviewed for approval in United States and Europe and may play a significant role

in patients with previously demonstrated SAMS (Statin-Associated Muscle Symptoms) in that

they lower LDL cholesterol via a different pathway. PCSK9 affects the ability of the LDL

Receptor to separate from the LDL after delivering LDL to the hepatocyte; PCSK9 inhibitors allow

the LDL Receptor to recycle thus be more effective in lowering the total LDL level. The first drugs

(manufacturers) to apply for approval are anticipated to be alirocumab (Sanofi/Regeneron),

evolocumab (Amgen) and bococizumab (Pfizer). All are expected to apply to the FDA for the

indication of “statin intolerance”. Effectiveness studies have shown a differential response likely

based on the underlying level of PCSK9 in individual patients, along with a variable response in

tolerance, including myalgias, when compared to standard therapy. These will be discussed along

with anticipated role for the PCSK9s in statin intolerant patients. Conclusion: PCSK9 inhibitors

offer a different mechanism than the HMG-CoA reductase inhibitors to lower LDL cholesterol and

may provide an opportunity to achieve LDL goals even in patients intolerant to HMG-CoA

reductase inhibitors due to SAMS.

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235

A LARGE PRAGMATIC TRIAL OF STATINS IN PRIMARY PREVENTION: THE

NEXT FRONTIER M.E. Farkouh, M. Domanski

1. Peter Munk Cardiac Centre, University of Toronto, Toronto, Canada

2. Icahn School of Medicine at Mount Sinai, New York, NY, USA

Atherothrombotic disease is the most common cause of death in the world. Pharmacologic LDL

lowering has been shown to reduce coronary heart disease (CHD) events according to the LDL

level achieved with no demonstrated level below which events do not decrease with additional

LDL lowering. Further, available data suggest that the earlier the LDL lowering occurs, the greater

the therapeutic effect of a given decrease.

Objective: The purpose of the proposed study (Elimination of Coronary Artery Disease [ECAD])

is to determine whether pharmacologic lowering of serum low density lipoprotein cholesterol

(LDL), initiated in healthy young to middle-aged adults, can eliminate, or markedly reduce CAD.

Study design: ECAD is a randomized, multicenter, primary prevention clinical trial designed to

compare a strategy of usual guideline based lipid management to a strategy of LDL lowering

medication (atorvastatin 20 mg daily) for the primary prevention of atherothrombotic events (all

cause death, excluding those due to cancer and trauma, myocardial infarction, stroke, or coronary

revascularization) in healthy middle aged men and women.

Study subjects are men 35 to 50 years of age and women of non-child bearing potential 45 to 59

years of age without any prior history of CHD, stroke, or peripheral vascular disease who have

one additional risk factor (hypertension and waist circumference >100 cm in men or >90 cm in

women, family history of premature coronary atherosclerosis, or smoking) and LDL from 1.8

mmol/l ( 70 mg/dL) to the minimum LDL for which the current ACC/AHA Guidelines recommend

pharmacologic treatment in the presence of a single additional risk factor.

Intervention or Treatment: Usual guideline-based therapy versus usual guideline-based therapy

with the addition of atorvastatin 20 mg daily.

Sample Size: A total of 15,000 patients will be recruited to participate in this trial from 300 primary

care practices.

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236

NOVEL BIOMARKERS OF LIPID AND LIPOPROTEIN METABOLISM

S. Mora

Brigham and Women's Hospital, Boston, MA, USA

Objectives: Cardiovascular disease (CVD) can occur in individuals with low LDL-cholesterol

(LDL-c). We investigated whether detailed measures of LDL subfractions and other lipoproteins

can be used to assess CVD risk in a population with both low LDL-c and high C-reactive protein

that was randomized to high-intensity statin or placebo.

Methods and Results: In 11,186 JUPITER participants, we tested whether lipids, apolipoproteins,

and ion mobility (IM)-measured particle concentrations at baseline and after random allocation to

rosuvastatin 20 mg/d or placebo were associated with first CVD events (n=307) or CVD/all-cause

death (n=522). In placebo-allocated participants, baseline LDL-c was not associated with CVD

(adjusted HR per SD, 1.03, 95% CI 0.89-1.20). In contrast, associations with CVD events were

observed for baseline non-HDL-cholesterol (non-HDL-c: 1.18, 1.02-1.37), apolipoprotein B

(apoB: 1.28, 1.11-1.49), and IM-measured non-HDL particles (non-HDL-p: 1.19, 1.05-1.36) and

LDL particles (LDL-p: 1.21, 1.06-1.38). Association with CVD events was also observed for

several LDL and VLDL subfractions, but not for IM-measured HDL subfractions. In statin-

allocated participants, CVD events were associated with on-treatment LDL-c, non-HDL-c, and

apoB; these were also associated with CVD/all-cause death, as were several LDL and VLDL

subfractions albeit with a pattern of association that differed from the baseline risk.

Conclusions: In JUPITER, baseline LDL-c was not associated with CVD events, in contrast with

significant associations for non-HDL-c and atherogenic particles: apoB and IM-measured non-

HDL-p, LDL-p, and select subfractions of VLDL-p and LDL-p. During high-intensity statin

therapy, on-treatment levels of LDL-c and atherogenic particles were associated with residual risk

of CVD/all-cause death.

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237

THE ROLE OF STATINS IN PREVENTION OF CONTRAST-INDUCED ACUTE

KIDNEY INJURY

M.A. Alpert

University of Missouri-Columbia School of Medicine, Columbia, MO, USA

Contrast induced acute kidney injury (CIAKI) is a common cause of acute renal failure in patients

undergoing coronary angiography and/or percutaneous coronary interventions (PCI). Patients at

risk for CIAKI include those with diabetes mellitus, renal insufficiency, heart failure, hypotension

and shock and those receiving nephrotoxic medications. Other risk factors include high volumes

of high-osmolality radiographic contrast media, anemia and use of an intra-aortic balloon pump.

Multiple pharmacologic and non-pharmacologic interventions have been studied in an attempt to

prevent this complication in at-risk patients. The most successful interventions to date are pre-

procedure, intravenous hydration using normal saline or sodium bicarbonate and use of non-ionic,

iso-osmolar radiographic contrast media. In recent years, there has been increasing interest in the

role of HMG-CoA reductase inhibitors (statins) in the prevention of CIAKI in patients undergoing

coronary angiography and/or PCI. Prior studies have involved patients on chronic statin therapy

and those receiving short-term (often high-dose) statin therapy prior to and following contrast

exposure. Patients studied include those with acute coronary syndromes and those undergoing

elective coronary angiography with or without PCI. A wide variety of hydrophilic and lipophilic

statins have been used. Non-randomized studies have, for the part, shown a reduction in the

incidence of CIAKI with statin use. Randomized clinical trials investigating this issue have

reported mixed results. Most, but not all have reported a decrease in the risk of CIAKI. Studies

showing a reduction in CIAKI risk include those employing short-term and long-term statin

therapy, high and low-dose statins as well as hydrophilic and lipophilic statins. The preponderance

of evidence suggests that statins are capable of reducing the risk of CIAKI in patients undergoing

coronary angiography and PCI.

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238

STATIN USE AND LIPID CONTROL BY ACC/AHA STATIN ELIGIBILITY GROUP

IN UNITED STATES ADULTS 2011-2012

N.D. Wong1, D. Young1, Y. Zhao1, H. Nguyen1, J. Caballes1, I. Khan2*, R.J. Sanchez3* 1. Heart Disease Prevention Program, Division of Cardiology, University of California, Irvine, CA, USA

2. Sanofi Pharmaceuticals, Bridgewater, NJ, USA

3. Regeneron Pharmaceuticals, Tarrytown, NY, USA

Background: The 2013 ACC/AHA Cholesterol Management Guidelines identify four statin

eligible groups, those with: 1) known atherosclerotic cardiovascular disease (ASCVD), 2) LDL-C

>190 mg/dl, 3) diabetes aged 40-75, and 4) primary prevention >7.5% 10-year ASCVD risk aged

40-75. We examined the number of potentially statin eligible US adults in these groups and the

current extent of statin therapy and lipid control based on prior guidelines.

Methods: We identified US adults aged >21 years from the US National Health and Nutrition

Examination Survey (NHANES) 2011-2012 in the above statin eligible groups and determined the

proportion of each on a statin prescription. Among those with LDL-C levels available, we also

determined the proportion at recommended LDL-C levels. NHANES 2-year sample weights were

applied to all estimates.

Results: Among a total of 5,206 adults representing 219 million persons, we identified 1,696 adults

representing 63 million adults which fit into one of the four statin eligible groups. The table below

notes the estimated number of US adults within each statin eligible group and proportion receiving

statin therapy, and who were at recommended LDL-C levels.

Conclusion: Significant proportions of US adults eligible to receive statins based on the

ACC/AHA guidelines are not taking statins and goal attainment is suboptimal.

Statin Eligible Group Sample

n

Weighted N

(millions)

% on

Statin

% at LDL-C

goal *

ASCVD 549 19.3 59.9 15.2

**LDL-C>190 mg/dl 53 2.6 19.3 n/a

Diabetes, all

ASCVD 10-year risk

<7.5%

>7.5%

444

187

257

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55.4

47.1

39.9

52.1

Primary Prevention

ASCVD 10-year risk>7.5%

650 27.2 28.8 62.0

* Among all subjects with LDL-C levels regardless of statin use: LDL-C goals for ASCVD: <70

mg/dl, Diabetes: <100 mg/dl, >=7.5% group: <130 mg/dl; n/a for LDL-C>190 mg/dl group since

defined on the basis of elevated LDL-C only. **Does not include persons on treatment but

controlled to LDL-C<190 mg/dl.

*This study was funded by a contract from Regeneron to the University of California, Irvine.

Dr Khan is an employee of Sanofi-Aventis Pharmaceuticals, Bridgewater, NJ and Dr. Sanchez is

an employee of Regeneron Pharmaceuticals, Tarrytown, NY.

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239

SUCCESSFUL ROLE OF CASCADE SCREENING IN FAMILIAL

HYPERCHOLESTEROLEMIA IN INDIAN POPULATION N. Setia1, J.P.S. Sawhney2, R. Saxena1, I.C. Verma1

1. Center of Medical Genetics, Sir Ganga Ram Hospital, New Delhi, Delhi, India

2. Department of Cardiology, Sir Ganga Ram Hospital, New Delhi, Delhi, India

Background: Familial Hypercholesterolemia (FH) is an inherited disorder of lipid metabolism

characterized by high low density lipoprotein (LDL) cholesterol since birth resulting in

atherosclerosis and premature coronary artery disease (CAD) and family history of early CAD.

FH is caused by mutations in LDL receptor, ApoB100 and PCSK9 gene. Frequency is estimated

to be 1 in 350.

Objectives: To identify carriers of FH mutations by Cascade screening of family members of

subjects positive for the mutation and provide appropriate interventions.

Results: Mutation screening was done in index cases with suspicion of FH. Modified Dutch Lipid

Network Criteria (DLNC) criteria was used to identify subjects which led to identification of 36

disease causing mutations (9 novel) in LDLR gene in 42 FH index cases. Ten cases out of 42 were

homozygous while 32 were heterozygous for a LDLR mutation. Of 42 index cases, 126 family

members were screened. 86 (68%) were found to harbor the mutation and had significantly higher

LDL cholesterol levels than the non mutation carrier family members. Of 86 affected family

members, 71 were adults (Mean age 37.8 years) and 15 were children (Mean age 12.3years). Out

of 86, 15 (17%) had CAD and 42 (48%) were already on lipid lowering therapy.

Conclusions: Cascade screening led to identification of 71 new cases who were at a very high risk

of developing premature CAD. Affected family members were referred to cardiology and

hyperlipidemia clinic for lifestyle modification and drug therapy, if required. It proved to be a

successful initiative towards primary prevention of CAD.

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PSYCHOMETRIC EVALUATION OF A TREATMENT ACCEPTANCE MEASURE IN

PATIENTS RECEIVING SUBCUTANEOUS INJECTION TREATMENT R.J. Sanchez1, L. Grant2, S. Tadlock2, R. Arbuckle2, I. Khan3, G. Manvelian1,

J.A. Spertus4

1. Regeneron Pharmaceuticals, Tarrytown, NY, USA

2. 2 Adelphi Values, Adelphi Mill, Bollington, Cheshire, United Kingdom

3. Bridgewater, NJ, USA

4. Mid America Heart Institute of Saint Luke’s Hospital and the University of Missouri, Kansas

City, MO, USA

Objectives: Alirocumab, a PCSK9 inhibitor, significantly reduces low density lipoprotein –

cholesterol, but requires subcutaneous injections rather than oral pills. To quantify patients’

acceptance of this treatment modality, a new patient reported outcome, the injection–treatment

acceptance questionnaire (I-TAQ), was developed and psychometrically evaluated with high

cardiovascular risk patients receiving alirocumab.

Methods: The 22-item, five domain, I-TAQ was developed through literature review and

qualitative patient interviews to confirm content validity. The measure was administered once to

151 patients enrolled in alirocumab clinical trials. Analyses conducted included evaluation of item

response distributions, factor and multi-trait analyses, inter-item correlations, correlations with an

existing measure of acceptance (convergent validity) and comparison of known groups.

Results: Completion rates were high with no patients missing >2 items and 91.4% with no missing

data. All items displayed high ceiling effects (>30% at ceiling) due to high treatment acceptance.

Factor analysis supported the a priori hypothesized item-domain structure with strong fit indices

(RMSEA= 0.070; CFI= 0.988). All items demonstrated strong item convergent validity (item-scale

correlation = >0.4), except for the side effects domain due to small response numbers (n=46). All

but two items correlated most highly with the domain they were included in (item discriminant

validity). Internal consistency reliability was strong for all domains (Cronbach’s alpha range: 0.72-

0.88). Convergent validity was supported by a logical pattern of correlations.

Conclusions: The newly developed I-TAQ has strong psychometric properties in patients treated

with subcutaneous alirocumab and should prove to be a valuable patient-reported outcome for

therapies requiring subcutaneous injection.

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CARDIOVASCULAR IMAGING MODALITIES FOR EVALUATION OF CORONARY CIRCULATION, CARDIAC STRUCTURE AND FUNCTION

241

EFFICACY OF SPECT/CT MPI VERSUS ADDITIONAL PRONE SPECT MPI FOR

ATTENUATION CORRECTION OF INFERIOR WALL DEFECTS W. Park1, P. Sarda1, K.L. Tsai1, K. Nallu2, I. Seo1, C. Nedelcu1

1. The Brooklyn Hospital Center, Brooklyn, NY, USA

2. Mount Sinai Beth Israel Medical Center, New York, NY, USA

Objective: To avoid extra radiation to the patient from SPECT/CT if there is no significant

difference between SPECT/CT and additional prone SPECT.

Background: When the patient has an enlarged heart, the heart may rest lower on the diaphragm

rather on the inner chest wall, so it can be difficult to determine whether the patient has a real

inferior wall infarct. To resolve this problem, attenuation correction (AC) by SPECT/CT or

additional prone SPECT can be performed.

Methods: Patients in the period from 1/1/2012 to 12/31/2014 who underwent MPI and additional

prone SPECT or SPECT/CT to evaluate inferior wall defects were recorded. Cases were excluded

if they had no inferior wall defects on MPI or there was no attempt at AC. We collected and

compared the results to determine efficacy between SPECT/CT and additional prone SPECT. We

also compared the results in patients with enlarged hearts; a cut-off value of 150 for left ventricular

end-diastolic volume was used.

Results: Out of a total of 1,086 cases, 681 received SPECT/CT and 405 received additional prone

imaging. 542 cases out of 681 had AC in SPECT/CT and 274 cases out of 405 had AC in additional

prone imaging (p<0.0001). In patients with enlarged hearts, 103 cases out of 157 from SPECT/CT

had AC and 34 cases out of 67 from additional prone imaging had AC (p=0.037). In patients with

normal heart sizes, 439 cases out of 524 from SPECT/CT had AC and 240 cases out of 338 from

additional prone imaging had AC (p<0.0001).

Conclusions: We conclude that SPECT/CT is significantly better than additional prone imaging

when AC is performed to detect inferior wall defects both in patients with enlarged hearts and

those with normal-sized hearts. Unless there are any contraindications, we recommend SPECT/CT

with AC when inferior wall defects are suspected.

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COMPARATIVE STUDY OF FFR, IFR AND PD/PA - IS THERE STILL A PLACE FOR

ADENOSINE USE IN THE CATH LAB? R. Placido, H. Correia, N. Cortez-Dias, T. Guimaraes, G. Lima da Silva, J.A. Duarte,

J. Marques da Costa, P. Canas da Silva, F. Pinto


Portugal

Introduction: Fractional flow reserve (FFR) is an hemodynamic index measured at maximum

adenosine induced hyperemia, validated for the functional assessment of coronary stenosis. Given

the potential complications and procedure delay, alternative methods without adenosine

administration have been investigated, including the instantaneous wave-free ratio (iFR) and the

resting distal coronary pressure to aortic pressure ratio (Pd/Pa).Objective: To evaluate the

diagnostic accuracy of iFR and Pd/Pa in the functional assessment of coronary stenosis when

compared to FFR.

Methods: observational study of patients undergoing coronary angiography with borderline

coronary lesions. iFR and Pd/Pa were measured. FFR was subsequently assessed during

intravenous administration of adenosine. Diagnostic accuracy was assessed by the area under the

receiver operating characteristic curve (AUC), considering < 0,80 as the FFR cut-off value for

hemodynamic significance.

Results: 72 borderline coronary stenosis were evaluated in 52 patients (71±10 years; 79% male).

FFR was highly correlated with iFR (Pearson R=0.77; p <0.001) and Pd/Pa (Pearson R=0.67; p

<0.001). iFR was found to have the best diagnostic accuracy (AUC=0.89; 95% CI 0.82-0.97 versus

Pd/Pa=0.81, 95% CI 0.69 to 0.93) for hemodynamic significance. Diagnostic thresholds were 0.90

and 0.93 for iFR and Pd/Pa, respectively. iFR validity stemmed from its high negative predictive

value in excluding angiographic hemodynamic significance for a >0.90 value (negative predictive

value: 91.8%; positive predictive value: 70.8%).

Conclusion: iFR assessment could be an intermediate step for interventional decision. An iFR

value >0.90 excludes an hemodynamically significant lesion. Notwithstanding FFR should be used

when in the presence of an iFR value below 0,90 as it does not assure functional significance.

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243

RELATIONSHIP OF DIASTOLIC FUNCTION AND MAXIMAL EXERCISE

CAPACITY AMONG PATIENTS WITH LOW RISK FOR CORONARY ARTERY

DISEASE: A RETROSPECTIVE CROSS-SECTIONAL STUDY M.T. Bayuga, R.E. Ramboyong

The Medical City, Pasig City, Philippines

Background: There is a significant correlation between exercise capacity and diastolic function

parameters in patients at high cardiovascular risk and with proven cardiovascular diseases. This

study aims to determine the relationship of diastolic function and maximal exercise capacity

among patients with low risk for CAD.

Methods: 189 patients were retrospectively studied who underwent stress echocardiography from

September 2013 until February 2014 at The Medical City. They were divided into two groups

according to their exercise capacity (METS). Group 1 with MET <7 and Group 2 with >7 MET.

Diastolic variables were mitral inflow velocities, early diastolic velocity (E), late diastolic velocity

(A), E/A ratio, E’ wave velocity, E/E’ ratio, isovolumetric relaxation time and left atrial volume

index.

Results: Among 189 patients, mean age was 45.7 ± 8.68 and mostly were male. Normal diastolic

function was observed in 67%; 30% showed grade 1 diastolic dysfunction and 3% showed grade

2 diastolic dysfunction. 16% had increased filling pressures. Clinical parameters that correlated

with a low functional capacity were female gender (p-value: 0.003), age (p-value: 0.006),

dyslipidemia (p-value: 0.026), family history of heart disease (p-value: 0.002) and a positive

treadmill exercise stress echocardiography (p-value: 0.022). In relation to the echocardiographic

parameters, A wave velocity (p-value: 0.000), E/A ratio of the mitral flow (p-value: 0.002), E’

wave velocity of the mitral annulus (p-value: 0.001) and the E/E’ ratio (p-value: 0.007) were

associated with MET < 7. The comparative analysis of the MET < 7 and MET > 7 groups in

relation to the presence of increased filling pressures (E/E’ > 10), 25.4% of patients with normal

functional capacity and 50% with low functional capacity had impaired left ventricular filling

pressure.

Conclusion: Diastolic dysfunction by echocardiography is associated with a low exercise capacity

even among patients with low risk for coronary artery disease.

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244

CORRELATION BETWEEN USCOM-DERIVED HAEMODYNAMIC VARIABLES

AND SEVERITY OF CHRONIC HEART FAILURE M.M. Lee1, N.M. Cheng2, T.H. Rainer2, L.T. So3, J.R. Mo4

1. University of British Columbia, Vancouver, Canada

2. The Chinese University of Hong Kong, Hong Kong

3. Princess Margaret Hospital, Hong Kong

4. The Second Affiliate Hospital of Guangzhou Medical University, Guangzhou, China

Background: Ultrasonic Cardiac Output Monitor (USCOM)-derived inotropy has been shown to

discriminate patients with New York Heart Association (NYHA) stage IV from healthy controls.

This study aims to investigate whether inotropy and other haemodynamic variables correlate with

NYHA class and ejection fraction (EF).

Methods: Ethical approval was obtained to conduct a prospective, single-centre, observational

study of patients presenting with heart failure symptoms to the echocardiography clinic at Prince

of Wales hospital. The echocardiography and USCOM assessments were conducted by separate

trained technicians who were blind to results from each other. The primary outcome was difference

in mean inotropy between NYHA classes I, II, III, and IV. Secondary outcome was correlation

between USCOM hemodynamic parameters and left ventricular ejection fraction (LVEF).

(Clinical trial no. NCT02289508)

Results: Between June 2014 and January 2015, a convenience sample of 117 subjects were

enrolled (NYHA Class I, n=28 (24%); Class II, n=58 (50%); Class III, n=22 (19%); Class IV n=7

(6%)). Differences between stroke volume index (SVI) and DO2 were found to be significant

across NYHA classes (p<0.05). Differences in inotropy, cardiac index (CI) and systemic vascular

resistance index (SVRI) were not significant. USCOM-SVI showed moderate correlation with

Echo-LVEF (r=0.41; p<0.01). USCOM-SVRI (r=0.30, p<0.01), USCOM-CI (r=.29, p<0.01), and

USCOM-inotropy (r=0.27, p<0.01) also showed weak to moderate correlation with LVEF.

Conclusion: The preliminary finding of this study shows that the USCOM-SVI and USCOM-DO2

correlated with NYHA stages of heart failure, and USCOM-SVI correlated with LVEF. The

preliminary finding of this study suggests a possible role of USCOM to augment bedside

assessment of patients with nonspecific heart failure presentation.

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245

THE ASSESSMENT OF CORONARY ARTERY CALCIFICATION IN HIGH-RISK

CORONARY ARTERY DISEASE POPULATIONS

M. Yacoub1, A. Makaryus2, D. Fridman3 J, Makaryus3,

1. Inspira Health Center, Vineland, NJ, USA

2. Nassau County Medical Center, East Meadow, NY, USA

3. North Shore University Hospital, Manhasset, NY, USA

Introduction: The detection of coronary artery calcification using multidetector computed

tomography is diagnostic of coronary artery disease (CAD) and arterial plaque burden. In addition,

the degree of coronary calcification is a powerful prognostic tool used to guide therapy and

management of patients at risk for coronary artery disease. We sought to assess patterns of

coronary artery calcification in a real-world patient population referred for CAC score

quantification to determine relative risk contribution for a variety of cardiovascular risk factors.

Methods: 138 Patients underwent unenhanced CT (120 KV, 100 mA, 3 mm slices) of the four

major coronary vessels, utilizing a standard CAC score protocol. coronary arterial calcification

and plaque burden.

Results: In total, 552 coronary arteries were evaluated in 138 patients. The mean age for females

was 64.4 years and for the males, 60.0. The calcium scores were measured at each of the four main

epicardial vessels. The odds of diabetic subjects having a total calcium score over 100 relative to

non-diabetic subjects was 5.64 times higher even after controlling for other cardiovascular risk

factors (95% CI: 1.49 to 21.31, p < 0.011). The odds ratios for a calcium score > 100 matched to

age, gender and smoking was also computed and yielded 1.12, 3.62 and 4.59, respectively, with

adjustment for other risk factors. Thus, diabetes mellitus and smoking, two potentially modifiable

risk factors, were by far the most contributory risk factors for the development of coronary

calcification.

Conclusion: Diabetes mellitus and smoking are acknowledged CAD risk factors resulting in both

micro- and macro-vascular complications. This may lead to alterations in the therapeutic approach

towards cardiovascular disease in diabetics and smokers, and reemphasizes the need to manage

these risk factors in particular before the occurrence of adverse cardiovascular events.

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OPTICAL COHERENCE TOMOGRAPHY IN ACUTE CORONARY SYNDROME O.S. Sandhu, B.K. Joshi

University of San Francisco Fresno, Fresno, CA, USA

This in-vivo study determined the novel imaging technique of optical coherence tomography can

be applied to the clinical setting to provide a more accurately defined morphology of coronary

plaque in acute coronary syndrome as compared to current imagining modalities, which will aid

in identifying the pathways in the etiopathogenesis of acute coronary syndrome; thus, the targeted

therapy can be established. This understanding may further help to prevent the occurrence of

coronary heart disease in the first place.

Of the 26 patients in this prospective study, plaque rupture was associated with acute coronary

syndrome in 61 percent of patients, while plaque erosion was seen in 39 percent of patients, which

is statistically significant (p <0.05). Additionally, fibrocalcific nodule was not seen in this early

stage of observational data. Plaque erosion was seen more commonly in women (60%) as

compared to men who have higher plaque rupture (69%) with statistical significance (p <0.05).

Smokers have higher incidence of plaque erosion (80%) as compared to plaque rupture (44%),

which is statistically significant (p <0.05). Patients with hypertension had higher incidence of

plaque rupture (81%) than plaque erosion (70%).

This study found: 1. Plaque rupture is more commonly associated with acute coronary syndrome

as compared to plaque erosion, 2. Women tend to have more plaque erosion as compared to men,

who tend to have plaque rupture, 3. Smokers have higher incidence of plaque erosion as compared

to plaque rupture, 4. Incidence of plaque rupture and plaque erosion did not differ based on the

involvement of the culprit artery, and 5. The presentation of ST segment elevation myocardial

infarction is more common in patients with plaque rupture, whereas non-ST segment elevation

myocardial infarction is more frequent in those with plaque erosion.

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CELLULAR AND MOLECULAR MECHANISMS OF CARDIOVASCULAR DISEASE, BASIC RESEARCH

248

DUAL HCM AND LQT1 PHENOTYPES ASSOCIATED WITH TETRAD

HETEROZYGOUS MUTATIONS IN MYH7, MYLK2, KCNQ1 AND TMEM70 GENES

IN A THREE-GENERATION CHINESE FAMILY

L.F. Wang1,2, Q. Yang1, L. Zuo1, J. Hu4, H. Shao5, C.H. Lei3, W. Qi1, C.L.H. Huang6, X.D.

Zhou1, Y.M Zhang7, L.W. Liu1 1. Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, Xi'an, China

2. Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China

3. Department of Ultrasound, Ningxia Medical University, Yinchuan, China

4. Department of Stomatology, the Military General Hospital of Beijing PLA, Beijing, China

5. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China

6. Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom

7. Heart Center, Northwest Women’s and Children’s Hospital, Xi'an, China

Contributed equally to this work.

Objective: Hypertrophic cardiomyopathy (HCM) mainly results from autosomal-dominant

inherited single heterozygous mutations in cardiac sarcomere genes. Contributions of multiple

gene mutations to disease heterogeneity in a three generation family was investigated.

Background: As a heterogeneous disease, HCM demonstrates phenotypic variation in the degree

of hypertrophy, arrhythmias, left ventricular outflow tract obstruction, even sudden death

susceptibility. Single mutation in cardiac sarcomere gene could not easily to explain.

Methods: Clinical, electrocardiographic (ECG) and echocardiographic examination in members

of a three-generation Chinese family was followed by exon and boarding intron analysis of 96

genes in the proband using second-generation sequencing. The identified mutations were

confirmed by bi-directional Sanger sequencing in all family members and 300 healthy controls.

Results and conclusions: Four missense mutations were detected in the family. These were two

novel MYH7-H1717Q and MYLK2-K324E mutations accompanied by the KCNQ1-R190W and

TMEM70-I147T mutations. The proband carried all four mutations and showed overlapping HCM

and LQT1 phenotypes. Five family members each carried two mutations. Subject II-2 only carried

TMEM70-I147T. MYH7-H1717Q and TMEM70-I147T came from the paternal side, whereas

KCNQ1-R190W and MYLK2-K324E came from the maternal side. Left ventricle mass indexes

in MYH7-H1717Q carriers were significantly higher than in non-H1717Q carriers (90.05 ±

7.33g/m2, 63.20 ± 4.53 g/m2 respectively, P<0.01). Four KCNQ1-R190W carriers showed QTc

intervals that were significantly more prolonged than those in non-R190W carriers (472.25 ± 16.18

ms and 408.50 ± 7.66 ms ms respectively, P<0.05). All MYLK2-K324E carriers showed inverted

ECG T waves. The subject with only a TMEM70-I147T mutation showed normal ECG and

echocardiographs suggesting that this had less pathological effects at least in this family. For the

first time, we demonstrate dual HCM and LQT1 phenotypes in this multiple HCM and LQT1

related gene mutation carrier family and suggest that LQT-related gene mutations associate with

QT interval prolongation and/or arrhythmia in HCM patients.

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249

GENETIC VARIABILITY IN PAR-1 DOES NOT AFFECT RISK OF BLEEDING OR

ISCHEMIA AFTER PERCUTANEOUS CORONARY INTERVENTION E.A. Friedman , L.C. Texeira, J.T. Delaney, P. Weeke, E.S. Kasasbeh, D.R. Lynch,

H.E. Hamm, D.M. Roden, J.C. Denny, J.C .Cleator

Vanderbilt University, Nashville, TN, USA

Objectives/Background: Platelet reactivity is associated with recurrent ischemia and bleeding

following percutaneous coronary intervention (PCI). Protease-activated receptor-1 (PAR-1),

encoded by F2R, is a high affinity thrombin receptor on platelets and the target of the antiplatelet

drug vorapaxar. The intronic single nucleotide polymorphism F2R IVS-14 A/T affects PAR-1

receptor density and function. We hypothesized that carriers of the T allele, who have decreased

platelet reactivity, would be at lower risk for ischemic events, but higher risk for bleeding

following PCI.

Methods: Using BioVU, the Vanderbilt DNA repository linked to the electronic medical record,

we studied 572 patients who underwent PCI for unstable or stable coronary artery disease. Primary

outcome measures were major adverse cardiovascular events (MACE, composite of

revascularization, MI, stroke, death) and bleeding (assessed by Bleeding Academic Research

Consortium scale) over 24 months.

Results: The minor allele (T) frequency was 15.0%. There were no genotypic differences in the

frequency of MACE or bleeding (Table 1). In a Cox regression model, fully adjusted for age, race,

sex, body mass index, and smoking status, carrying a T allele was not associated with MACE (HR

1.19, 95% CI 0.89-1.59, P=0.23) or bleeding (HR 0.73, 95% CI 0.37-1.4, P=0.34).

Conclusion: In our population, F2R IVS-14 PAR-1 variability does not affect risk of MACE or

bleeding following PCI.

Table 1: Frequency of Major Adverse Cardiac Events or Bleeding Stratified by F2R IVS-14

Genotype

GENOTYPE

A/A (n=416)

A/T (n=140)

T/T (n=16)

P value

MACE, n (%) 161 (38.7%) 49 (35.0%) 6 (37.5%) 0.62

BLEEDING, n (%) 66 (15.8%) 19 (13.6%) 3 (18.8%) 0.76

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250

GENETICS AND HYPERTENSIVE HEART DISEASE. STUDY ON THE

RELATIONSHIP BETWEEN 5HT2A AND HYPERTENSIVE HEART DISEASE T.G. Onojighofia1,2, N. Anand1, B. Akindele1, D. Schwarz1,3, S. Kantorovich1,

B. Meshkin1, M. Hafez1, M. Hopkins1

1. Proove Biosciences, Irvine, CA, USA

2. Johns Hopkins University, Baltimore, MD, USA

3. Pain Recovery

Background: Many different types of heart diseases run in families and can be inherited. Though

the role of lifestyle in heart disease is clearly understood, little is known on the role played by

genetics. Since heart disease remains the number one killer in the U.S, the need to better understand

the role of genetics in risk of heart disease has become very important.

Objective: The study objective is to determine if any association exists between genetics and

hypertensive heart disease.

Subjects: 85 subjects across 8 clinical research sites in the US. 42 diagnosed with hypertensive

heart disease (ICD9 codes 401(Essential hypertension), and 401.9 (Hypertension Unspecified).

Mean Age 49, Males 27, Females 16, and 43 controls matched for age, race and gender.

Methods: Subjects were genotyped using Taqman® SNP Genotyping Assays (Life Technologies,

Carlsbad, CA). It consists of a panel of 12 single nucleotide polymorphisms (SNPs) in genes

encoding for proteins expressed in the mesolimbic reward pathway. These genes include: 5HT2a,

5-HTTL, COMT, ANKK1/DRD2, DRD1, DRD4, DAT, DBH, MTHFR, OPRK1, GABA-A

receptor gamma2, and OPRM1.

Results: A chi-square test using IBM SPSS V21 found significant association between 5-HT2a -

1438G/A (rs7997012) and hypertensive heart disease: Over dominant Model (G/A vs. G/G-A/A)

p= 0.036, Two sided fisher’s exact 0.047). Logistic regression (p= 0.035) showed that G/A

variation is more likely to be associated with subjects with hypertensive heart disease compared

to the controls. (p= 0.038, OR, 2.583). Significant association was found between male subjects

and hypertensive heart disease subjects (p= 0.002 OR 4.219).

Conclusion: This study suggests that 5-HT2a (rs7997012) may play a role in genetic predisposition

to hypertensive heart disease. Findings in this study will hopefully help improve understanding on

the role of genetics in heart disease.

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EFFECT OF GENE DELIVERY PLASMID ENCODING INTERLEUKIN-19 ON RAT

EXPERIMENTAL AUTOIMMUNE MYOCARDITIS H. Chang1,2 , Y. Wang1,2, G. Li1,2, J. Zou1

1. Xiamen University Medical College, Xiamen, China

2. Xiamen Heart Center, Xiamen, China

Objectives: To evaluate the effect of gene delivery plasmid encoding Interleukin-19 on rat

Experimental Autoimmune Myocarditis (EAM) and possible mechanism.

Background: IL-19 is a novel, recently identified member of the IL-10 family, however, little is

known about the exact biological role in immunological regulation.

Methods: The rat was immunized on day 0 and were injected with plasmid encoding IL-19 on day

6, all the rats were sacrificed on day 17. The effect of IL-19 gene delivery was evaluated by

measuring of heart weight/body weight and myocarditis area, The relative gene expression levels

of heart failure markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were

detected by real-time RT-PCR. Cardiac Function were performed by Echocardiography.

Furthermore, we examined the effect of serum containing IL-19 on the expression of immune-

relevant genes in IL-1-stimulated Spleen cells cultured from EAM rats.

Results: IL-19 gene therapy was effective in controlling EAM as monitored by decreased ratio of

heart weight / body weight and the myocarditis area, The level of ANP and BNP were significantly

lower and cardiac function parameters improved in IL-19 treatment group than those in control

group. The serum containing IL-19 significantly decreased the expression of IL-18, IL-1beta, IL-

12p35, IFN-gamma and upregulated IL-4 and IL-10 expression in IL-1-stimulated spleen cells

cultured from EAM rats.

Conclusion: IL-19 effectively prevented progression of EAM by blocking related inflammatory

immune genes expression. This might be a possible mechanism of the amelioration of EAM by

IL-19 gene therapy.

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252

VAGAL ACTIVATION BENEFITS FOR CELLULAR CALCIUM HOMEOSTASIS IN

CARDIOVASCULAR DISEASE M. Zhao, X. He, X.Z. Lu, X.Y. Bi, X.J. Yu, Y. Yang, W.J. Zang

Department of Pharmacology, Xi’an Jiaotong University Health Science Center, Xi'an, Shaanxi,

P.R. China

Background: A hallmark of cardiovascular disease (CVD) is impaired cytoplasmic calcium

handling of cell. Previous studies showed that increasing vagal tone ameliorated cardiovascular

damages. Nevertheless, the effects of vagal activation to the calcium regulation are unclear.

Objectives: The present studies investigated whether vagal activation benefited for cellular calcium

homeostasis in CVD.

Methods: The in vivo ischemia/reperfusion (I/R) and in vitro hypoxia/reoxygenation (H/R) models

were adopted. Vascular function, calcium concentration and protein expression were detected by

a myograph system, confocal microscopy and western blot, respectively. Specific protein

knockdown was performed with siRNA.

Results: Our studies demonstrated that acetylcholine (ACh) significantly ameliorated

dysfunctional vasoconstriction and reduced calcium-sensing receptor expression and activity in

H/R arteries. Choline, a muscarinic ACh receptor agonist, markedly improved abnormal

expression of calcium-cycling proteins though inhibiting calcium-calmodulin-dependent kinases

in I/R arteries. These effects of vagal activation may be contributed to depress cytoplasmic calcium

overload. In addition, we observed that ACh inhibited the formation of endoplasmic reticulum-

mitochondria junctions to attenuate mitochondria calcium overload in H/R endothelial cells,

indicating that ACh is involved in inter-organellar calcium transport. Furthermore, we paid

attention to the calcium downstream signaling. Results showed that ACh could suppress apoptosis

of myocardial cells via inhibition of calpain and calpastatin.

Conclusion: ACh not only depress cytoplasmic calcium overload, but also reduced calcium

downstream proteic activity and endoplasmic reticulum-mitochondria communication. Our

findings firstly clarified the potential roles of vagal activation in calcium regulation, and further

help to develop novel therapeutic strategies targeting enhancing vagal activity for the treatment of

CVD.

Supported by: grant from National Natural Science Foundation of China (Major International Joint

Research Project, No. 81120108002; General Project, No. 81473203), Specialized Research Fund

for the Doctoral Program of Higher Education (No. 20130201130008).

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253

GLUCOSE TOLERANCE AND NON-FASTING GLUCOSE ARE BETTER

PREDICTORS OF ATHEROSCLEROSIS THAN INSULIN RESISTANCE OR

FASTING GLUCOSE IN APOE-/- STAINS W. Shi, S. Liu, J. Li, Z. Liu

University of Virginia, Charlottesville, Virginia, USA

A major reason behind poor understanding on diabetes-accelerated atherosclerosis is the lack of

appropriate animal models. We recently found that apolipoprotein E-deficient (Apoe-/-) with the

C57BL/6 background develop type 2 diabetes and accelerated atherosclerosis on a Western diet.

Multiple Apoe-/- mouse strains were made to discover diabetes-related phenotyptic variations that

might predict atherosclerosis development. Evaluation of both early and advanced lesion

formation in aortic root revealed that C57BL/6, SWR, and SM Apoe-/- mice were susceptible to

atherosclerosis and C3H/HeJ and BALB/cJ Apoe-/- mice were relatively resistant. On a chow

diet, fasting plasma glucose varied among strains with C3H/HeJ having the highest and BALB/cJ

the lowest level. On a Western diet, fasting plasma glucose rose significantly in all strains, with

C57BL/6, C3H/HeJ and SWR exceeding 300 mg/dl. BALB/cJ and C3H/HeJ were more tolerant

to glucose loading than other 3 strains. C57BL/6 was sensitive to insulin while other strains were

resistant. Non-fasting blood glucose was significantly lower in C3H/HeJ and BALB/cJ than

C57BL/6, SM, and SWR. Glucose loading induced the 1st and the 2nd phase of insulin secretion

in BALB/cJ, but the 2nd phase was not observed in other strains. Morphological analysis showed

that BALB/cJ had the largest islet area and C57BL/6 had the smallest one. These findings indicate

that glucose tolerance and non-fasting glucose are better predictors of atherosclerosis than insulin

resistance or fasting glucose in Apoe-/- stains.

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254

THE INFILTRATING MACROPHAGE-SECRETED GALECTIN-3 PLAYS

ESSENTIAL ROLE IN PRESSURE OVERLOAD-INDUCED CARDIAC FIBROSIS VIA

CTGF EXPRESSION J-J Chen1,3, W-R Hao2, K-C Chang1, J-C Liu2

1. Department of Internal Medicine and Graduate Institute of Clinical Medical Science, China

Medical University, Taichung, Taiwan

2. Taipei Medical University- Shuang Ho Hospital, Division of Cardiology, Department of

Medicine, New Taipei City, Taiwan

3. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

Background: Cardiac fibrosis is the major pathophysiological process, contributing to the

development of diastolic heart failure. We examine the role of macrophage-derived galectin-3 (gal-

3) in cardiac fibrosis in response to transverse aortic constriction (TAC) and elucidate the

underlying molecular mechanism.

Method : Wild-type (WT) and gal-3 knock-out (KO) mice subjected to TAC,

immunohistochemistry for assessment of myocardial macrophage infiltration,gal-3,and CTGF

(connective tissue growth factor) expression, picrosirius and Masson stains for myocardial fibrosis,

MTT and Brdu incorporation assays for cell proliferation, flow-cytometry analysis for cell

differentiation, co-immunoprecipitation and confocal microscopy for lectin-carbohydrate

interaction and co-localization respectively.

Result: WT mice after TAC showed significant increase of myocardial macrophage infiltration,

gal-3 and CTGF expression, fibroblast proliferation/differentiation, and interstitial fibrosis,

compared with sham-operated animals (n=10, p<0.01). Macrophage depletion or gal-3 Knock-out

markedly suppressed myocardial fibrosis and vice versa. In in-vitro, co-immunoprecipitation and

confocal microscopy confirmed gal-3-EGFR interaction and co-localization on cell membrane.

Treatment with recombinant gal-3 increased EGFR and downstream ERK phosphorylation, and

CTGF expression in cultured cardiac fibroblasts or their gal-3 knock-down cells. Moreover, using

MTT and Brdu incorporation assays either direct addition of recombinant gal-3 or co-culture with

macrophages significantly promoted cardiac fibroblast proliferation via CTGF expression.

Conclusion: Pressure-overload promotes myocardial macrophage infiltration and the infiltrating

macrophage -secreted gal-3 cross-links with its cell surface glycoconjugate, EGFR, resulting in its

autophosphorylation, activation of subsequent mitogenic ERK signaling, myocardial CTGF

expression, fibroblast proliferation/differentiation and myocardial fibrosis. Our findings provide

molecular basis for gal-3 as a potential therapeutic target in heart failure.

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255

IDENTIFICATION OF ASPIRIN RESPONSE RELATED GENE PROFILES IN CAD

PATIENTS OLDER THAN 50 YEARS J.W. Zhang1, T.F. Liu1, X.H. Chen1, X.R. Feng1, L. Wang2, W.Y. Liang1, S. Fu3,

T. McCaffrey3, M.L. Liu1

1. Department of Geriatrics, Peking University First Hospital, Beijing, China

2. Peking University Center for Human Disease Genomics, Department of Immunology, Health

Science Center, Peking University, Beijing, China

3. Department of Medicine, The George Washington University Medical Center, Washington

DC, USA

Aims: The phenomenon that responses to aspirin response vary from one patient to another has

aroused lots of concern. Recent studies observed that aspirin exposure lead to changes in

expression of various genes. The aim of our study was to identify aspirin response related gene

profiles, and to investigate the roles of multiple factors in promoting cardiovascular events.

Methods: An observational and prospective study of CAD patients older than 50 years on 100mg/d

aspirin were enrolled since January 2014. Hospitalization and follow-up records were collected.

Cardiovascular events were defined as the occurrence of myocardial infarction, stroke,

cardiovascular death and/or revascularization during regular aspirin therapy. Besides, whole blood

samples were collected for further total RNA extraction. Expression of fourteen genes (CLU

CMTM5 CTTN MPL TMEM64 SELP HLA-DQA1 HLA-DRB4 ITGA2B ITGB3 THBS1

CXCL5 PPBP SPARC) were measured using real-time quantitative PCR method.

Results: A total of 190 CAD patients older than 50 years were enrolled, with an average age of

77.01± 7.75. HAPR( high on aspirin platelet response) was defined as 0.5 mmol/L AA-induced

platelet aggregation ≥15.17%——upper quartile of the enrolled population. Eight genes (MPL HLA-

DQA1 HLA-DRB4 ITGA2B CLU CMTM5 SELP SPARC) were differentially expressed in

HAPR group. Besides, COX regression analysis showed that previous PCI history, co-morbidities

including diabetes and hypertension contributed to the occurrence of cardiovascular events, while

statins administration significantly reduce its risk. Expression of ten genes (CTTN ITGB3 CLU

THBS1 PPBP SPARC SELP TMEM64 CMTM5 HLA-DQA1) were potential risk factors in

predicting future cardiovascular events.

Conclusion: The eight differentially expressed genes in HAPR group might help distinguish

patients with poor aspirin responses. Besides, previous PCI history, co-morbidities including

diabetes and hypertension contributed to the occurrence of cardiovascular events, while statins

administration was proved to be protective. Expression of ten genes might help distinguish high

risk CAD patients.

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SYSTEMIC AND PULMONARY HYPERTENSION – RISK AND MANAGEMENT

256

DUAL AT1 RECEPTOR/NEPRILYSIN INHIBITION (ARNI) VS. AT1 RECEPTOR

BLOCKADE IN DIABETIC TGR(MREN2)27 RATS A.H.J. Danser, L.C.W. Roksnoer, W.W. Batenburg

Erasmus MC, Rotterdam, The Netherlands

The combination of an Angiotensin Receptor blocker (ARB) and a Neprilysin Inhibitor (NEPi)

has beneficial effects on clinical progression and mortality of heart failure patients as compared to

enalapril. However, since NEP also degrades endothelin-1 (ET-1), ARNI may cause side-effects

by increasing ET-1. Indeed, we recently observed in hypertensive TGR(mREN2)27 rats that a low

but not a high dose of the NEPi thiorphan reduced blood pressure and cardiac hypertrophy on top

of the ARB irbesartan (IRB). This was due to the fact that the high dose increased ET-1,

upregulated constrictor vascular ET-1 type B receptors and induced an increase in renal sodium–

hydrogen exchanger 3 protein abundance. In the present study, we evaluated the effects of the low

thiorphan dose on top of IRB in TGR(mREN2)27 rats, made diabetic with streptozotocin for 5 or

12 weeks. Rats were treated in the final 3 weeks with vehicle, IRB or IRB +thiorphan (ARNI).

Haemodynamics were measured by telemetry in the 5-week diabetic animals. In the 12-week

diabetic animals vascular reactivity was determined in mesenteric arteries, renal Na+-transporters

were analysed by immunoblotting, and plasma and urine were collected for biochemical analysis.

Baseline mean arterial blood pressure (MAP) was 157±5 mmHg. IRB and ARNI lowered MAP

identically over the 3-week period, a maximum reduction of approximately 50 mmHg being

reached around day 7. Heart weight/tibia length ratio was reduced after treatment with ARNI only.

Proteinuria and albuminuria were observed from 8 weeks of diabetes onwards and proteinuria was

significantly reduced by ARNI treatment only. Urinary volume and plasma and urinary creatinine

did not change. No ET-1 rises were observed, vascular reactivity was not influenced, and the

pattern of kidney sodium transporters was not affected by ARNI or IRB treatment. Conclusion:

ARNI reduces cardiac hypertrophy and proteinuria in diabetic TGR(mREN2)27 rats independently

of blood pressure.

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257

GI PROTEIN AS POTENTIAL TARGET FOR THE TREATMENT OF

HYPERTENSION

M.B. Anand-Srivastava

Faculty of Medicine, University of Montreal, Montreal, QC, Canada

Guanine nucleotide regulatory proteins (G proteins) play an important role in the regulation of a

variety of physiological functions including blood pressure through the activation of different

effectors. We have previously shown an overexpression of inhibitory G proteins (Gialpha proteins)

in spontaneously hypertensive rats (SHR) and other models of hypertensive rats. The enhanced

expression of Gialpha proteins precedes the development of hypertension in SHR and DOCA-salt

hypertensive rats. Treatment of prehypertensive SHR with pertussis toxin that inactivates both

Gialpha-2 and Gialpha-3 proteins prevented the development of hypertension in SHR suggesting

the implication of enhanced expression of Gialpha proteins in the pathogenesis of hypertension.

In the present study, we investigated if both the Gialpha-2 and Gialpha-3 proteins are implicated

in the development of hypertension and used the antisense (AS) approach. The knockdown of

Gialpha-2 protein by Gialpha-2 AS prevented the development of hypertension up to 6 weeks of

age, thereafter it started increasing and reached the same level at 9 weeks as that of untreated SHR.

On the other hand, the treatment of SHR with Gialpha-3 AS did not significantly attenuate the

increased BP. Furthermore, the levels of Gialpha-2 and Gialpha-3 proteins in heart, kidney and

aorta from 6 week-old SHR treated with Gialpha-2-AS and Gialpha-3-AS were significantly

decreased compared to control SHR. However, these treatments did not attenuate the increased BP

and overexpression of Gialpha-2 and Gialpha-3 proteins in 9 week-old SHR. Furthermore,

treatment of prehypertensive SHR with C-ANP4-23; an agonist of natriuretic peptide receptor-C

(NPR-C) and resveratrol, attenuated the development of hypertension and overexpression of

Gialpha proteins in heart and aorta. These results suggest that Gialpha-2 protein plays an important

role in the development of hypertension in SHR and that the new therapies targeting Gialpha

proteins may be developed for the treatment of hypertension (Supported by grant from CIHR).

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258

NEW OUTCOME-BASED RECOMMENDATIONS FOR IMPROVING

HYPERTENSION DIAGNOSIS AND TREATMENT TO REDUCE RISK OF

VASCULAR EVENTS R.C. Hermida, D.E. Ayala

University of Vigo, Vigo, Spain

Diagnosis of hypertension and clinical decisions regarding its treatment are typically based upon

clinic blood pressure (BP) measurements, occasionally supplemented by wake-time patient self-

assessment. Yet, correlation between BP level and target organ damage, cardiovascular disease

(CVD) risk, and long-term prognosis is greater for ambulatory BP monitoring (ABPM) than

daytime in-clinic measurements. Additionally, consistent evidence of numerous studies

substantiates the ABPM-determined asleep BP mean is an independent and stronger predictor of

CVD risk than the awake or 24h means. Most importantly, when the asleep BP mean is adjusted

by the awake mean, only the former is a significant independent predictor of CVD outcome. The

MAPEC Study, first prospective randomized treatment-time investigation testing the worthiness

of bedtime hypertension treatment to specifically target attenuation of asleep BP, not only

documents the asleep BP mean is the most significant prognostic marker of CVD and stroke

morbidity and mortality, but it also substantiates attenuation of the asleep BP mean significantly

reduces CVD risk, both in the general hypertension population and in patients of greater

vulnerability and enhanced CVD risk, i.e., those diagnosed with chronic kidney disease, diabetes,

and resistant hypertension. Preliminary findings from the Hygia Project, a multicenter,

prospective, controlled study designed to evaluate the prognostic value of ABPM and that has

recruited so far >16,000 subjects who undergo periodic, at least annual, 48h ABPM evaluation,

corroborates sleep-time systolic BP mean, but not daytime clinic BP measurement or ABPM-

derived awake BP mean, is the only significant and independent prognostic marker of CVD

morbidity and mortality. These collective findings indicate: (i) CVD risk assessment should be

based on ABPM, mainly of asleep systolic BP, as a new gold standard; and (ii) pharmacologic

intervention in hypertension should take into account the variable of treatment-time to properly

reduce asleep BP as a novel therapeutic target.

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RESISTANT HYPERTENSION: DIAGNOSTIC AND TREATMENT ISSUES D.E. Ayala, R.C. Hermida

University of Vigo, Vigo, Spain

By current definition, hypertension is considered resistant to treatment when lifestyle measures

plus ingestion of at least 3 hypertension medications, one preferably a diuretic unless

contraindicated, in therapeutic doses fail to reduce systolic and diastolic blood pressure (BP) to

recommended clinic thresholds. However, published reports document the correlation between BP

level and target organ damage, cardiovascular (CVD) risk, and long-term prognosis is far greater

for ambulatory BP monitoring (ABPM) than clinical BP measurements. An increasing number of

studies document sleep-time BP is abnormally elevated in most patients with resistant

hypertension thereby indicating diagnosis of true resistant hypertension cannot be decided solely

by comparison of office BP with either wake-time patient BP self-measurements or awake BP

mean from ABPM, as so far customary in the published literature. Moreover, the ABPM-

determined asleep BP mean is an independent and stronger predictor of CVD risk than either

daytime office and ABPM-derived awake or 24h means. Results of the recently completed

prospective outcome MAPEC Study that included a large cohort of patients with resistant

hypertension, establish treatment time, relative to the rest-activity cycle of each individual patient,

constitutes a critically important, yet often neglected, variable regarding BP control; bedtime

compared to morning ingestion of the full dose of at least one BP-lowering medications results

both in better therapeutic normalization of sleep-time BP and reduced CVD morbidity and

mortality, including in patients with resistant hypertension. Collectively, recent findings of the

above cited and other prospective studies indicate a bedtime hypertension medication regimen, in

conjunction with proper patient evaluation by ABPM to corroborate the diagnosis of true resistant

hypertension, should be the therapeutic scheme of choice for patients who, by conventional cuff

methods (and in the absence of the application of ABPM) and an inappropriate morning-treatment

regimen, may have been mistakenly judged to be resistant to therapy.

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260

MYOCARDIAL INTERSTITIAL DISARRAY AND CARDIOVASCULAR APOPTOSIS

AND REMODELING IN PULMONARY HYPERTENSION DYSPNEA,

COMPLICATED WITH LATE INFECTION

I. Angomachalelis1,2, G. Kyriazis1, D. Vassilakos2, N. Angomachalelis1

Aristotle University of Thessaloniki: 1Department of Internal Medicine, Heart-Lung Section, ”G. Papanikolaou” General Hospital 2Department of Critical Care and Anaesthesiology, AHEPA University Hospital, Thessaloniki,

Macedonia, Greece

Purpose: The study aims to investigate unknown pathophysiology of myocardial interstitial

disarray, arising from Metalloproteinase-2 (MMP-2) activity in Pulmonary Hypertension (PH)

dyspnea patients (Pts), correlated with serum Procalcitonin (PCT) levels and other Biomarkers.

Methods: 55 PH dyspnea Pts, 34 males and 21 females (mean age 68±14 years) and 33, matched

control, normal individuals, were submitted to 1) Serum evaluation of PCT, MMP-2, Troponin-I

(Tr-I), Erythropoietin (EPO) and NT-ProBNP. 2) Clinical, ECG, Chest X-ray and Computed

Tomography (CT) examination, 3) Pulmonary Function Tests (PFTs), Arterial Blood Gasses

(ABGs) and Blood tests, 4) Echocardiography.

Results: The results Showed: 1)Abnormal serum values of PCT=0.39 ng/ml, MMP-2=376 ng/ml,

Tr-I=2 ng/ml, EPO=26 m/U/ml, NT-ProBNP=4.242 pg/ml, 2) Restrictive impairment of

pulmonary function tests and hypoxemia with extremely increased alveolo-arterial oxygen

difference [P(A-a)02]= 49mmHg, 3) Normal ejection fraction (EF), left atrial and right ventricular

enlargement (LAD,RVID), RVSP=52 mmHg, 4) Primary significant correlation of MMP-2 with

a) PCT (r=0.630), b) Tr-I (r=0.390), c) EPO (r=-0.340), d) PCO2(r=0.340), and e) NT-ProBNP

(r=0.310), 5) Statistical correlations of any significance were not confirmed with ABGs, excluding

PCO2.

Conclusions: We conclude that: 1) Serum MMP-2 activity on the grounds of PH dyspnea is

obviously leading to myocardial interstitial disarray, arising mainly from the related serum PCT

presence, expressing original contribution of an infective reaction pathophysiology. 2) The related

serum Tr-I, EPO and NT-ProBNP values indicate existence of myocardial cell apoptosis and

congestive remodeling, due to PH of cardiac origin, possibly co-induced from PCT infective

reaction, 3) However, the infection related PCO2 levels looks contributing to myocardial interstitial

fibrosis, further possibly connecting with inflammation and Thrombogenesis, 4) PFTs and the rest

of ABGs do not seem correlated with infection induced pathophysiology of MMP-2 activity in PH

dyspnea.

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261

ADVANCES IN THE THERAPY OF PULMONARY ARTERIAL HYPERTENSION

R.C. Bourge The University of Alabama at Birmingham, AL, USA

Pulmonary arterial hypertension is a group of diseases, probably with a genetic predisposition and

possibly an environmental trigger, leading to elevated pulmonary arterial tree resistance, right

heart failure, and a generally poor prognosis. Since the development of intravenous epoprostenol

as the first approved therapy for pulmonary arterial hypertension, multiple agents have been and

are being investigated. Based on the pathophysiology of the disease(s), therapies have been

developed that affect the three main pathways believed responsible for arterial vasodilation: the

endothelin pathway, the nitric acid pathway, and the prostaglandin pathway. These drugs act

largely by stimulating receptors leading to vasodilation, blocking receptors that lead to

vasoconstriction, and/or lessen vessel wall cell wall proliferation. Work is also done on

compounds that may reduce vessel wall inflammation in these diseases. These medical therapies

include oral, transdermal, inhaled, and intravenous delivery options. For some, the combination

of these therapies may have the capability to transform the lives of our patients from that with a

poor prognosis and the need for the continuous or frequently administered therapy, to a life with

an almost “forgettable” disease, at least in terms of day to day activities.

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262

PROGNOSTIC STRATIFICATION IN PULMONARY HYPERTENSION: A MULTI-

BIOMARKER APPROACH R. Placido1, N. Cortez-Dias1, S.R. Martins1, E. Gayat2, S. Goncalves1,

E. Infante Oliveira1, M. Sadoune2, A.G. Almeida1, A. Mebazaa2, F. Pinto1

1. Hospital Santa Maria, Serv Cardiologia I, Lisbon Academic Medical Centre, CCUL, Lisbon,

Portugal

2. Department of Anesthesiology and Intensive Care, Lariboisiere University Hospital,

Assistance Publique-Hopitaux de Paris, Universite Paris Diderot, Paris, France

Introduction: Pulmonary hypertension (PH) is associated with an increase in pulmonary vascular

resistance leading to right ventricular failure. Risk stratification is crucial for adequate prognostic

and therapeutic assessment. However, the accuracy of the conventional parameters is limited,

specially regarding to biomarkers.

Objectives: Determine the prognostic value of new biomarkers and their combination in a

multibiomarker approach to predict outcome in patients with PH.

Methods: Prospective cohort study of patients with PH. Patients underwent clinical,

echocardiographic and laboratory evaluation, including quantification of serum NT-proBNP and

the following new biomarkers: MR-proADM, copeptin, endothelin-1, MR-proANP and soluble

interleukin-33 receptor (ST2). The accuracy of different parameters in the prediction of death from

any cause and death or hospitalization for cardiac causes was determined. The prognostic value of

a multibiomarker score based on the tertile distribution of serum NT-proBNP, MR-proANP, renin

and ST2 was tested.

Results: Forty-three patients (72.1% female; 59±15 years) were included. Most patients (65.1%)

had group 1 PH. During a median follow-up of 34 months, 26% of patients died and 35% were

hospitalized for cardiac causes. NT-proBNP (log) [HR: 31.14; 95% CI: 3.12 to 310.7; P=0.003)]

and renin (HR: 1.02; 95% CI: 1.005 to 1.038; P=0.009) were independent predictors of mortality.

MR-proANP (HR: 1.008; 95% CI 1.004 to 1.011; P <0.001) and ST2 (HR: 1.005; 95% CI 1.001

to 1.009; P = 0.04) were predictors of death or hospitalization. The prognostic value of the

multibiomarker score was higher than any of the conventional parameters, allowing the

identification of risk groups (high risk group with a mortality at 3 years of 77.8%).

Conclusion: a multibiomarker strategy provided superior risk stratification beyond any single-

marker approach. The score that incorporates NT-proBNP, MR-proANP, renin and ST2 accurately

identifies patients with low, intermediate and high risk.

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263

MORTALITY IS HIGHER BUT NOT DIFFERENT AMONG RESISTANT

HYPERTENSION PATIENT COHORTS DEFINED BY DIFFERENT CRITERIA O.W. Odunukan1, D.M. Filsoof1, D.O. Hodge2, A.B. Schultz2, M.A. Nyman3,

V.T. Nkomo4

1. Division of Cardiology, Mayo Clinic Jacksonville FL, USA

3. Division for Health Services Research, Robert D. and Patricia E. Kern Center for the Science

of Health Care Delivery, Mayo Clinic, Rochester MN, USA

3. Division of General Internal Medicine, Mayo Clinic Rochester MN, USA

4. Division of Cardiology, Mayo Clinic Rochester MN, USA

Background: The implications of the use of different definitions for resistant hypertension on

survival outcomes have not been fully determined.

Purpose: To compare survival among cohorts of resistant hypertension patients defined by current

working definitions.

Methods: Using hypertension medications from outpatient visits notes in 2009, 2 cohorts of

resistant hypertension patients were built using current definitions. Patients with BP 140 over 90

mmHg and above despite a 3 drug regimen including a diuretic were classified as uHTN and those

on 4 or more hypertension drugs to maintain BP control were labelled as cHTN. The two groups

were compared with known patients with hypertension (kHTN).

Results: Survival at 4 years was 79.1% with 317 deaths and 1169 censored patients, (unadjusted

hazard ratio HR 3.29, p<0.0001) in the uHTN cohort and 78.8 % with 356 deaths, 1274 censored

patients (HR 3.33, p<0.0001) in the cHTN group compared to 93.3% in the kHTN cohort with 665

deaths and 8341 censored patients. After adjusting for age, sex, atrial fibrillation/flutter, heart

failure, CKD, CAD, acute myocardial infarction, stroke, obesity, diabetes, sleep apnea and

pulmonary hypertension, HR was 1.83, p<0.0001 for uHTN and 1.66, p<0.0001 for cHTN

compared to the kHTN group. There was no difference in survival between the uHTN and cHTN

cohorts (unadjusted HR 0.99, p<0.89) although cardiovascular comorbidities were more prevalent

in the cHTN group.

Conclusion: Although survival was worse resistant hypertension patients compared to known

hypertension patients, there was no apparent difference among the 2 cohorts of resistant

hypertension as defined by contemporary criteria.

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264

LEFT ATRIAL ENLARGEMENT AS A PREDICTOR OF PULMONARY

HYPERTENSION IN PATIENTS WITH DIASTOLIC DYSFUNCTION P. Rodriguez-Lozano, S. Raslan, A. Melhem, M. Shea, A. Khan, P. Nalabothu,

M. Morsy, W.I. Khalife, K. Sadat


Background: Pulmonary Hypertension (PH) is a frequent complication of left heart disease. The

development of PH in patients with left heart disease is associated with poor prognosis. Objective:

To investigate predictive factors for PH in patients with diastolic dysfunction (DD).

Methods: We retrospectively analyzed echocardiograms of 1,584 patients performed at a

University hospital. Patients were classified into normal (n=529, 33.4%) & those with DD

(n=1055, 66.7%), including Impaired Relaxation (IR, n=869, 54.9%), Pseudonormal (PN, n=161,

10.2%), & Restrictive pattern (Res, n=25, 1.6%). To investigate predictive factors for PH

(RVSP>40) in patients with diastolic dysfunction (DD).

Results: In patients with DD, we found 17.4% with PH vs 82.7% with no PH p<0.0001. The

presence of PH is more frequent in IR (55.8%) vs control (24.9%), but not for the two higher levels

of DD (15.4% & 4.0%, respectively). There is a significant difference in presence of PH among

the levels of DDX severity, with the highest being 40% for DDX=3, and decreasing for each lower

level (29.2% for DDX=2, 14.5% for DDX=1 and 9.8% for DDX=0). In the multivariate (logistic

regression) analysis, we examined LA volume (or LA index), Pro BNP and DD as predictors for

Pulm HTN(RVSP>40). LA volume is a predictor for Pulm HTN (RVSP) with an OR=1.020, 95%

CI=1.012-1.028, p<0.0001. Also LA volume is associated with Pulm HTN in patients with

Pseudonormal DD (stage 2) vs control (OR=1.016, 95%CI=1.008-1.025, p<0.0001).

Conclusions: In patients with PH adjusting for Pro BNP and DD, LA enlargement can be a

predictor factor for development of PH.

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265

PREVALENCE OF HYPERTENSION AND DIFFERENCE OF BLOOD PRESSURE

CONTROL BETWEEN METABOLICALLY OBESE NORMAL BODY WEIGHT

(MONW) AND METABOLICALLY HEALTHY OBESE BODY WEIGHT (MHO) IN

HIV POPULATION H.S. Lee, A. Sy, A. Savadkar, T. Lenox, K. Kadeishvili

New York Medical College, New York, NY, USA

Objective: The aim of this study is to identify the prevalence of hypertension in these two groups

of HIV-infected patients as well as to investigate the relative success of blood pressure control, in

a community hospital in East Harlem, New York.

Background: Research has shown that HIV patients can become metabolically unhealthy and/or

obese just as other non-HIV infected patients, but also secondary to their illness or and/or its

treatment. However, the prevalence of hypertension and its control in MONW and MHO HIV-

infected patients has until now not been systematically studied.

Methods: 472 HIV patients were identified in the registry of Metropolitan Hospital Center from

January, 2012 to December 2014. Retained cases were assigned to either the metabolically-obese-

normal-weight (MONW) group or the metabolically-healthy-obese (MHO) group as defined by

the National Cholesterol Education Program–Adult Treatment Panel (NCEP–ATP) III definition

of metabolic syndrome. We applied the JNC 8 Hypertension blood pressure guidelines. All data

were analyzed using SAS Ver. 9.4.

Results: 466 patients were included in the study. Normal weight group was 36.1%, overweight

group was 34.2% and obese group was 29.7%. Prevalence of hypertension was 33.3% among

MONW and 5.7% among MHO. Mean systolic blood pressure was 129.1±18 mmHg and diastolic

blood pressure was 76.9±10 mmHg in MONW, 118.1±13 mmHg and 70.1±9.8 mmHg in MHO.

MONW cases showed statistically non-random associations with uncontrolled blood pressure as

compared to MHO cases [Odds ratio (OR): 0.018, 95% Confidence Interval (CI): 0.003-0.119].

Female sex [OR: 6.5, 95% CI: 1.447-29.208] and high LDL [OR: 6.08, 95% CI 1.148-32.245] was

found to be the risk factors for uncontrolled blood pressure for both groups.

Conclusions: MONW HIV patients are more prone to uncontrolled blood pressure and require

more intensive blood pressure management and strategies to diminish cardiovascular

complications than MHO HIV patients.

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ACUTE CORONARY SYNDROME: DETECTION, PREVENTION AND TREATMENT

266

LONG-TERM EFFECTS OF ISCHEMIC POSTCONDITIONING ON CLINICAL

OUTCOMES J.Y. Hahn1, C.W. Yu2, H.S. Park3, Y.B. Song1, J.H. Oh4, W.J. Chun4

1. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

2. Korea University Anam Hospital, South Korea

3. Kyungpook National University Hospital, South Korea

4. Samsung Changwon Hospital, Sungkyunkwan University School of Medicine,

South Korea

Background: In the Effects of Postconditioning on Myocardial Reperfusion in Patients with ST-

segment Elevation Myocardial Infarction (POST) trial, ischemic postconditioning failed to

improve myocardial reperfusion. However, long-term effects of ischemic postconditioning on

clinical outcomes are not known in patients with ST-segment elevation myocardial infarction

(STEMI).

Methods: A total of 700 patients undergoing primary percutaneous coronary intervention (PCI)

were randomly assigned to the postconditioning group or the conventional primary PCI group in

a 1:1 ratio. Postconditioning was performed immediately after restoration of coronary flow by

balloon occlusion 4 times for 1 minute. Complete follow-up data for major clinical events at 1 year

were available in 695 patients (99.3%) and analyses were done by the intention-to-treat principle.

The primary outcome was a composite of death, myocardial infarction, severe heart failure, or

stent thrombosis at 1 year.

Results: At 1 year, a composite of death, myocardial infarction, severe heart failure, or stent

thrombosis occurred in 21 patients (6.1%) in the postconditioning group and 16 patients (4.6%) in

the conventional PCI group (hazard ratio [HR] 1.32; 95% confidence interval [CI] 0.69–2.53;

P=.40). The risk of death (4.9% versus 3.7%; HR 1.32; 95% CI 0.64–2.71; P=.46), heart failure

(2.6% versus 2.3%; HR 1.13; 95% CI 0.44–2.94; P=.80), and stent thrombosis (2.3% versus 1.7%;

HR 1.34; 95% CI 0.46–3.85; P=0.59) did not differ significantly between the 2 groups.

Conclusions: Ischemic postconditioning does not seem to improve the 1-year clinical outcomes in

patients with STEMI undergoing primary PCI.

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267

ELECTROCARDIOGRAPHIC LEFT ATRIAL ENLARGEMENT AS AN

INDEPENDENT PREDICTOR FOR IN-HOSPITAL HEART FAILURE IN PATIENTS

WITH NON-ST ELEVATION MYOCARDIAL INFARCTION A. Kobayashi, N. Misumida, Y. Kanei, J. Fox

Mount Sinai Beth Israel Medical Center, New York, NY, USA

Background: Electrocardiographic left atrial enlargement is frequently observed in various

cardiovascular diseases. Enlarged left atrial determined by echocardiography has been shown to

predict adverse cardiovascular events. However little is known about the prevalence and

prognostic value of electrocardiographic left atrial enlargement among patient with Non-ST

Elevation Myocardial Infarction.

Methods: We performed a retrospective analysis of 481 consecutive patients with NSTEMI who

underwent coronary angiography. Patients with atrial fibrillation and atrial-paced rhythm were

excluded. Enlarged left atrial on the electrocardiogram was defined as either P-wave

duration>120ms in 2 lead or P-terminal force in lead V1>40ms•mm. Baseline and angiographic

characteristics, in-hospital heart failure as well as in-hospital major adverse cardiac event (MACE)

including death, recurrent myocardial infarction, and target vessel revascularization were

compared between the two groups.

Results: Among 452 patients, 142 patients (31.4%) had electrocardiographic left atrial

enlargement. There was no significant difference in age, or in the rate of history of previous

myocardial infarction or previous revascularization procedures between patients with and without

electrocardiographic left atrial enlargement. Patients with electrocardiographic left enlargement

had a higher left ventricular end-diastolic pressure (LVEDP) (20 [14-27] mmHg vs. 18 [14-23]

mmHg, p=0.037) and a lower left ventricular ejection fraction (LVEF) (55% [37-60] vs. 60% [45-

65], p=0.013). Patients with electrocardiographic left atrial enlargement had a higher incidence of

in-hospital heart failure (28.9% vs. 9.0%, p<0.001). There was no significant difference in the rate

of in-hospital MACE between the two groups. By multivariable analysis, electrocardiographic left

atrial enlargement was an independent predictor of in-hospital heart failure after adjusting for age,

LVEDP and LVEF (odds ration 4.1; 95% confidence interval 1.88 to 9.02; p<0.001).

Conclusion: Electrocardiographic enlarged left atrial was associated with lower LVEF and higher

LVEDP in patients with NSTEMI. By multivariate analysis, electrocardiographic enlarged left

atrial was an independent predictor of in-hospital heart failure.

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268

COMPLETE REVASCULARIZATION IN ACUTE MYOCARDIAL INFARCTION IS

SAFE AND WITHOUT MORE REINTERVENTIONS: STRATEGY DEFERRED VS.

INDEX PROCEDURE J.M. Telayna, J.M.H. Telayna, R.A. Costantini

Hospital Universitario Austral, Pilar, Argentina

Introduction: Forty percent of patients treated with primary angioplasty (PCI) have multi vessel

disease (MVD) an independent mortality predictor. It is reported that during an acute coronary

syndrome (ACS), a diffuse inflammatory process in which multiple plaques with complicated

atheroma takes place.

Objective: To analyze clinical outcomes of complete deferred revascularization (during the same

hospitalization or within 30 days) vs. the index procedure in PCI.

Method: Population: From May 2000 to December 2014, 374 consecutive pts with AMI were

treated, 189 of whom had MVD. Same session CR was done in 58 pts (group A), while deferred

CR in 35 pts (group B). Baseline characteristics: mean age 58 ± 11 vs 57 ± 9 years, diabetes 15

(29%) vs 7 (20%); previous infarction 6 (10) vs 6 (17); Killip Kimball C - D 9(15) vs 1(3) p=0.08;

IIbIIIa using 3(5) vs 9(26) p= 0.008; door to balloon time 110±60 vs 107±59 minutes; anterior

descending artery unrelated to infarction 21(36) vs 1(3) p=0.0001; initial TIMI 0 32(55) vs 21(60);

DES 10(17) vs 6(17); thromboaspiration 4(7) vs 6(17), radial access 21(36) vs 16(46), fluoroscopy

time 19.2±15 vs. 16.9±13 minutes; dye material 267.3±91 vs 236±98 milliliters.

Results: In-hospital: final TIMI III 58(100) vs 31(88) p=0.03, blush TIMI 3 final 52(90) vs 30(85)

p=0.8; cardiac death 2(3) vs 0 p=0.5; reinfarction 1(2) vs 0 p=0.7. At follow-up 18 ± 21.8 vs 23.9

± 18 months cardiovascular death 0 vs 1(3) p=0.3; reinfarction 2(4) vs 2(6) p=0.6, rePCI novo

lesions 3 (7) vs 2(6) p=1 and restenosis rePCI 2(4) vs. 3(8) p=0.3.

Conclusion: In our practice, we try to implement early CR in AMI. This "aggressive" strategy

showed no increased clinical risk for patients without penalizing with more re-interventions at

follow up.

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269

FIXED DOSING OF UNFRACTIONATED HEPARIN IN ST-ELEVATION

MYOCARDIAL INFARCTION TO IMPROVE DOOR-TO-PCI TIME

K. Narala, S. Banga, A. Aggarwal, H. Ghadiam, J. Heslop, S. Mungee

Department of Cardiology, University of Illinois College of Medicine at Peoria, Illinois, USA

Background: Weight based unfractionated heparin (UFH) dosing is used as initial therapy for ST-

elevation myocardial infarction (STEMI).

Objectives: We evaluated the effects of using a fixed dose UFH dose in patients undergoing

primary percutaneous coronary intervention (PCI) for STEMI.

Methods: We analyzed 270 consecutive patients that underwent primary PCI for STEMI. Patients

were given 4000 IU of UFH on presentation. The use of bivalirudin, additional UFH and

glycoprotein IIb/IIIa inhibitor (GPI) was at operator discretion. Patients were reclassified based on

weight based dose: Group 1 (< 50 U/kg), Group 2 (50-70 U/kg), and Group 3 (> 70 U/kg). Primary

outcomes were the 30-day rate of death, myocardial infarction, stent thrombosis, TIMI major

bleeding and a composite end point of major adverse composite events (MACE).

Results: There was no significant difference in MACE after adjusting for confounding variables

using logistic regression analysis by age, gender, diabetes, hyperlipidemia or bivalirudin use

(Table 1).

Conclusions: Standardized heparin dosing resulted in an door-to-PCI time of 52 minutes. There

was no difference in adverse outcomes when analyzed for weight. Utilizing a simplified fixed

heparin dose allows for significantly shorter reperfusion times without compromising clinical

outcomes. Table 1. Patient Demographics & Clinical Outcomes

Group 1 (N=164) Group 2 (N=88) Group 3 (N=16) P value

Age (years) 58 ± 12 64 ± 13 70 ± 13 <0.0001

Male 134 (81.7%) 56 (63.6%) 3 (18.8%) <0.0001

Diabetes 48 (29.3%) 13 (14.8%) 4 (25%) 0.03

HTN 116 (70.7%) 56 (63.6%) 12 (75%) 0.43

Smoking 83 (50.6%) 36 (40.9%) 8 (50%) 0.33

Hyperlipidemia 105 (64%) 51 (58%) 15 (93.8%) 0.02

Bivalirudin 81 (49.4%) 26 (29.5%) 2 (12.5%) <0.001

GPI use 63 (38.4%) 42 (47.7%) 8 (50%) 0.29

Outcomes

Myocardial

Infarction

3 (1.8%) 0 0 0.38

Stent thrombosis 5 (3%) 0 0 0.19

Death 7 (4.3%) 2 (2.3%) 2 (12.5%) 0.16

TIMI Major

Bleeding

2 (1.2%) 0 0 0.52

Cardiovascular

Death

6 (3.7%) 2 (2.3%) 1 (6.2%) 0.67

MACE 13 (7.9%) 2 (2.3%) 2 (12.5%) 0.12

Door to PCI time

(min)

52.1 ± 17.6 52.5 ± 15.6 50.6 ± 19.3 0.92

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270

EARLY VERSUS DELAYED INVASIVE STRATEGY FOR NON-ST SEGMENT

ELEVATION ACUTE CORONARY SYNDROME: A META-ANALYSIS OF

RANDOMIZED CONTROLLED CLINICAL TRIALS

K.A. Shaikh, M. Gedela, A. Stys, N. Rajpurohit

University of South Dakota, Sanford Heart Hospital, Sioux Falls, South Dakota, USA

Objective: To compare early versus delayed invasive strategy in high risk patients with Non-ST

segment elevation acute coronary syndrome (NSTE-ACS).

Background: Some early trials showed a benefit of early PCI in patients with non ST segment

elevation acute coronary syndrome(NSTE-ACS) but later on bigger randomized controlled trials

did not indicate clear benefit of early percutaneous coronary intervention (PCI) (<24 hours) in

patients with (NSTE-ACS) as compared to delayed PCI(>24 hours). Nonetheless recent data

suggests benefit of early PCI in high risk NSTE-ACS patients. We put together existing data and

performed meta-analysis.

Methods: Medline, PubMed and abstracts from major cardiology conferences were searched.

Randomized control trials (RCTs) comparing the composite of death and/or myocardial infarctions

(MI) and/or repeat revascularization within 6 months of early or delayed PCI for high risk patients

with NSTE-ACS were included. High risk was defined as TIMI score >5 or GRACE score >140.

The effects of both methods were analyzed by calculating pooled estimates for death, MI and

repeat revascularization. Analyses were performed for the outcome by using odds ratio (OR) by

random effects model. Heterogeneity among studies was assessed by calculating I″ measure of

inconsistency.

Results: We merged the data from four studies (ACUITY, ELISA-3, TIMACS and SISCA). Total

of 3259 patients who met our inclusion criteria were included. The incidence of the composite of

death and/or MI and/or repeat revascularization was lower in early PCI group [209/1505(13.8%)]

delayed PCI [331/1754(18.8%)] (OR 0.58 CI-0.35-0.97, P=0.002)

Conclusion: Contrary to the previous meta-analysis, our results indicate that early invasive strategy

(<24 hours) in high risk patients with TIMI>5 or Grace >140 does reduce the incidence of the

composite of death and and/or MI and/or repeat revascularization within 6 months.

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IMPROVING SURVIVAL AFTER TREATMENT FOR ST-ELEVATION

MYOCARDIAL INFARCTION - A 16 YEAR JOURNEY FROM 1997 TO 2013 J.M. Elliott1,2, D. Keown2, R. Lane2, J.W.H. Blake1, D.R. McClean1, A. Puri1,

D.W. Smyth1

1. Department of Cardiology, Christchurch Hospital, Christchurch, New Zealand

2. Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand

Objectives and Background: There have been major changes in the evidence based treatment of

ST-elevation myocardial infarction (STEMI) over the last 20 years including direct percutaneous

intervention (DPCI). But do the improved outcomes demonstrated in clinical trials also occur in

all-comer clinical populations?

Methods: Retrospective audit of STEMI patients admitted to our Department from Oct 1 through

Dec 31 in 1997-2002, 2006, 2010 and 2013. Baseline characteristics, in-hospital investigations,

discharge medications and one year outcomes were compared between years.

Results: In 2013, there were 59 STEMI patients, median age was 67 years, 76% men, 25% current

smokers, 22% had diabetes and 19% had previous MI. DPCI was performed in 51(86%): of the

other 8 patients, 3 presented >24 hours after onset of symptoms and 2 received PCI before

discharge, 1 refused DPCI, 2 had extensive co-morbidities, and the diagnosis was missed in 2 but

both received PCI before discharge. DPCI rates were 78% in 2010, 67% in 2006, 22% in 2001/02

and 7% in 1997/98. One year after discharge, Death or Death/Myocardial infarction occurred in

7.4% and 9.3% in the 2013 cohort compared with 8.8% and 10.3% in 2010, 10% and 12% in 2006,

13% and 18% in 2001/02 and 18% and 24% in 1997/98, p<0.01, chi-square.

Conclusion: Between 1997 and 2013, increased use of DPCI and evidence based medications have

resulted in an 11% absolute increase in survival and a 25% absolute increase in survival free from

repeat myocardial infarction one year after STEMI.

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272

CONTEMPORARY TROPONIN USE IN A LARGE US HOSPITAL SYSTEM K. Barkley1, B. Pope2, R. Kowal2, J.B. Michel1

1. Baylor Scott and White, Temple, Texas, USA

2. Baylor Scott and White, Dallas, Texas, USA

Background: Troponin measurement is integral to the diagnosis of acute coronary syndromes

(ACS). Current guidelines recommend assessing troponin in patients with possible ACS followed

by serial measurement if the initial value is normal. We sought to assess current clinical utilization

of Troponin in a large Hospital system.

Methods: All encounters for which troponin was assayed were recorded from 13 Hospitals in a

large US healthcare system from June 2013 to June 2014. When available, each Troponin value

was associated with a primary encounter diagnosis.

Results: Troponin was assayed in a total of 98,811 patient encounters. Primary diagnoses were

available for 93,436 encounters. There were 179,239 Troponin measurements, an average of 1.81

per encounter. 147,051 (82.1%) measurements were considered normal. However, 59,897

(33.4%) of normal Troponins were not followed by serial measurements. 21% of encounters had

a possible ACS diagnosis. Positive troponins were found in 8% of these encounters. There was

significant heterogeneity in Troponin values in the remaining 79% of patient encounters. No

positive troponins were found in encounters associated with primary diagnoses of Hypertension,

Dizziness, Abdominal Pain, Anxiety, Dehydration and Headache (6127 total encounters). Several

primary encounter diagnoses, however, where associated with higher rates of positive troponins

than were associated with a primary diagnosis of ACS, including CVA (10% of 865), septicemia

(26% of 1976) and acute respiratory failure (28% of 626).

Conclusion: We find evidence that troponin measurement in practice deviates significantly from

current guidelines and is often positive in clinical scenarios unlikely to represent ACS.

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273

DOES THROMBUS ASPIRATION IMPROVE CLINICAL OUTCOMES IN ST

ELEVATION MYOCARDIAL INFARCTION? H.K. Abbas, N. Sareen, M. Degregorio, K. Patel

St. Joseph Mercy Oakland Hospital, Pontiac, Michigan, USA

Introduction: Multiple studies including TAPAS trial suggested improved 1-year cardiac

outcomes, resulting in a guideline recommendation and substantial increase in routine

thrombectomy utilization. On the contrary, TASTE and TOTAL trials have been negative. We

sought to investigate this controversy by evaluating STEMI clinical outcomes with thrombectomy

utilization in real world patient population at our community hospital.

Aim: To compare 90 day rehospitalization and repeat revascularization rates with routine thrombus

aspiration before angioplasty compared to angioplasty alone in patients presenting with ST

elevation myocardial infarction.

Methods: Retrospective chart review of 100 consecutive patients above age of 18 years with

diagnosis of STEMI between 1/2013-1/2014 at our center was performed. We compared 90 day

rehospitalization and revascularization rates in patients who underwent thrombectomy followed

by angioplasty to angioplasty alone.

Results: No significant demographic differences were seen between the two groups. Of the 100

patients included in this study, 60 patients had angioplasty alone and 40 patients had thrombectomy

followed by angioplasty. There was no significant difference observed in the 90 day

rehospitalization rate in the two groups. 90 day repeat revascularization rates were also similar in

the two groups. These differences persisted at different levels of thrombus grades seen during the

index coronary angiography.

Conclusion: Our study revealed no difference in rehospitalization and repeat revascularization

rates with utilization of thrombus aspiration in STEMI patient population at our hospital. Our study

is a single center study and results are hypothesis generating.

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MOLECULAR AND CELLULAR CARDIOLOGY / VASCULAR BIOLOGY, BASIC RESEARCH

274

IN VIVO PROTEASE-ACTIVATED RECEPTOR -1 MEDIATED CORONARY

VASOREACTIVITY CORRELATES WITH PAR-1 EXPRESSION DISTRIBUTION IN

THE CORONARY VASCULAR WALL E.S. Kasasbeh, S.A. Phillips, L. Couhtino, P. Williams, A.H. Nunnally, J. Adcock,

L. Wang, H.E. Hamm, J.H. Cleator

Vanderbilt University Medical Center, Nashville, TN, USA

In humans, in vivo Protease Activated Receptor -1 (PAR-1) activation increases forearm blood

flow, however, the in vivo effects of PAR-1 activation on coronary vascular tone in any species is

unknown. Therefore we conducted a study evaluating the in vivo effects of PAR-1 activation in

the canine and porcine coronary vasculature. To study the in vivo effects of canine PAR-1 agonist

peptides on the canine coronary vasculature, we first established the effects on canine platelets and

in isolated canine coronary microvascular endothelial cells (CCAMECs). PAR-1 agonist peptide

failed to activate canine platelets, but dose-dependently increased intracellular calcium levels in

CCAMECs. To examine the in vivo PAR-1 response, PAR-1 agonist peptide was infused into

canine and porcine coronaries and coronary diameters were measured and coronary blood flow

(CBF) and coronary vascular resistance (CVR) were calculated from doppler-derived velocities.

Intracoronary infusion of PAR-1 agonist peptide caused a dose-dependent statistically significant

decrease in coronary diameter in the canine accompanied by a statistically significant decrease in

CBF and an increase in CVR. In contrast, in vivo administration of PAR-1 agonist peptide in the

porcine coronary vasculature increased CBF and decreased CVR. Immunostaining of coronary

arteries demonstrated that PAR-1 expression is more highly expressed in the media of the vascular

wall in the canine, while largely limited to the coronary endothelium in the porcine. In conclusion,

in vivo PAR-1 agonist peptide resulted in platelet-independent vasoconstriction of both canine

epicardial coronary arteries and the canine coronary microvasculature. In contrast, PAR-1- agonist

peptide vasodilated the porcine coronary microvasculature. The difference in vasoreactivity

between the species correlates with the expression pattern of PAR-1 in the coronary vascular wall.

These results describing the off-target platelet effects of PAR-1 activation on the coronary

vasculature may partly explain the discrepant results observed with PAR-1 antagonism observed

in clinical trials.

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275

EXTRACELLULAR HSP27 AND TLR4 ATTENUATE FUNCTIONAL RECOVERY IN

AGING MOUSE HEARTS FOLLOWING ISCHEMIA L. Ao, Y. Zhai, J.C. Cleveland, D.A. Fullerton, X. Meng

University of Colorado Denver, Aurora, CO, USA

Objectives: The aim of this study was to determine the role of extracellular heat shock protein

(HSP) 27 and Toll-like receptors (TLRs) in cytokine production and functional injury caused by

ex vivo global ischemia/reperfusion (I/R) in aging hearts.

Background: While cardiac functional recovery is poor in the elderly following cardiac surgery

with obligatory global myocardial I/R, the underlying mechanism remains incompletely

understood. We found recently that human and mouse myocardium releases HSP27 during global

I/R, and extracellular HSP27 plays a role in post-ischemic inflammatory response in adult mouse

hearts.

Methods and Results: Isolated hearts from aging (18-24 months) and adult (4-6 months) mice were

perfused by the Langendorff system and subjected to global normothermic I/R (20 min/120 min).

Augmented release of HSP27 in aging hearts preceded greater production of cytokines (MCP-1,

KC, IL-6 and TNF-alpha) and worse functional recovery. Anti-HSP27 suppressed the

inflammatory response and markedly improved functional recovery in aging hearts. Perfusion of

recombinant HSP27 to aging hearts resulted in greater cytokine production and contractile

depression. TLR2 KO and TLR4 deficiency, particularly the latter, markedly reduced cytokine

production and contractile dysfunction in aging hearts exposed to recombinant HSP27.

Interestingly, aging hearts had higher TLR4 protein levels and displayed enhanced TLR4-mediated

NF-kappaB activation.

Conclusion: The enhanced myocardial inflammatory response to global I/R in aging mouse hearts

is due, at least in part, to augmented myocardial release of HSP27. Extracellular HSP27 up-

regulates myocardial cytokine production and depresses cardiac contractility through TLR2 and

TLR4. Augmented HSP27 release and elevated myocardial TLR4 levels jointly play an important

role in the enhanced inflammatory response and worse post-ischemic functional recovery in aging

hearts.

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276

VASONATRINPEPTIDE ATTENUATES MYOCARDIAL ISCHEMIA/REPERFUSION

INJURY IN DIABETIC RATS AND UNDERLYING MECHANISMS

W.Z. Wang, Z.W. Shi, F. Fu, L.M. Yu, K. Wang, X.Y. Liang, H.F. Zhang

Experiment Teaching Center, Fourth Military Medical University, Xi’an, China

Objectives: This study was designed to investigate the effects of the artificial synthetic natriuretic

peptide — vasonatrin peptide (VNP) on myocardial ischemia/reperfusion (MI/R) injury in diabetic

rats and its mechanisms.

Background: Diabetes mellitus (DM) increases morbidity/mortality of ischemic heart disease.

Although the ability of the natriuretic peptides to modulate cardiac function and cell proliferation

has already been recognized, their effects on MI/R injury, especially in diabetic state, is still

unclear.

Methods: The high-fat diet-fed streptozotocin induced diabetic rats were subjected to MI/R (30

min/4 h) and VNP treatment (100 µg/kg, i.v., 10 min before R).

Results: The diabetic state aggravated MI/R injury and showed more severe myocardial functional

impairment than normal state. VNP treatment significantly improved ± LV dP/dtmax and LVSP,

and decreased infarct size, apoptosis index, caspase-3 activity, serum CK and LDH levels.

Moreover, VNP inhibited endoplasmic reticulum (ER) stress by suppressing GRP78 and CHOP,

and consequently increased the antiapoptotic protein Akt and ERK1/2 expression and

phosphorylation levels. These effects were mimicked by 8-Br-cGMP, a cGMP analogue, whereas

inhibited by KT-5823, the selective inhibitor of PKG. Pretreated DM rats with TUDCA, a specific

inhibitor of ER stress, couldn’t promote the VNP’s cardioprotection. In additional experiments

H9c2 cardiomyocytes were subjected to hypoxia/reoxygenation and incubated with or without

VNP. Gene knockdown of PKG1α with siRNA blunted VNP’s inhibition of ER stress and

apoptosis, while overexpression of PKG1α resulted in significant decreased ER stress and

apoptosis.

Conclusions: VNP protects diabetic heart against MI/R injury by inhibiting ER stress via cGMP-

PKG signaling pathway.

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277

CTRP1 OVEREXPRESSION INDUCES HYPERTENSION THROUGH SMOOTH

MUSCLE CONTRACTION S. Han, Y. Yang

Department of Life Science, Sookmyung Women's University, Seoul, South Korea

We previously reported that CTRP1 stimulates aldosterone production by upregulating the

transcription of cytochrome P-450 11beta-hydroxylase 2 (Cyp11b2), which is a rate-limiting

enzyme for aldosterone production. Because the previous study was performed in vitro, here, the

physiological role of CTRP1 in blood pressure (BP) regulation was investigated in vivo.CTRP1

transgenic (TG) mice showed a hypertensive phenotype without changes to cardiac, vascular, and

renal structures and hypertensive patients showed a significant increase in circulating CTRP1

levels. CTRP1 treatment significantly increased the contracting force in the aortic ring. In MOVAS

cells, CTRP1 activated the Rho/Rho kinase (ROCK) pathway, thereby leading to increased myosin

light chain (MLC) phosphorylation and intracellular Ca2+ levels. On the other hand, hypertension

was rescued in CTRP1 TG mice by the administration of inhibitors of renin (ramipril), angiotensin-

converting enzyme (nifedipine), angiotensin II receptor 1 (AT1R; losartan), and aldosterone

receptor (spironolactone). CTRP1 did not bind to AT1R; instead, CTRP1 induced AT1R

membrane localization. To identify factors that induce CTRP1 production, WT mice were treated

with various stressors; mice treated with acute electric foot shock showed elevated circulating

CTRP1 levels and increased BP. CTRP1 induces vasoconstriction by increasing intracellular Ca2+

levels and inducing AT1R trafficking to the plasma membrane. Acute psychological stress also

increases circulating CTRP1 levels, indicating the potential role of CTRP1 as a novel stress-

mediated vasoconstrictor. Thus, CTRP1 could be a novel therapeutic target for the development

of anti-hypertensive drugs.

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278

ACETYLCHOLINE REDUCES INFLAMMATORY AND ISCHEMIC INJURY BY

INHIBITING ENDOPLASMIC RETICULUM STRESS X.Y. Bi, Y. Miao, M. Zhao, X.J. Yu, X. He, M. Xu, W.J. Zang

Department of Pharmacology, Xi’an Jiaotong University Health Science Center, Xi’an, Shannxi,

PR China

Background: Endoplasmic reticulum (ER) stress plays an important role in regulation of protein

homeostasis and cell death. Acetylcholine (ACh), the neurotransmitter of vagal nerve, exerts

beneficial effect in cardiovascular diseases. However, little information is available on the

influence of ACh on ER stress.

Objectives: This study was designed to evaluate the effect of ACh on ER stress in response to

inflammatory and ischemic injury.

Methods: Using models of tumor necrosis factor alpha (TNF-alpha)-stimulated H9c2 cells and

hypoxia/reoxygenation (H/R)-injured endothelial cells, we examined the protein changes of ER

stress sensors by western blot. Cell apoptosis was shown by TUNEL. The structure of ER was

analyzed with transmission electron microscopy.

Results: Our results showed that (1) TNF-alpha stimulation increased index of ER stress (GRP78,

CHOP) and TUNEL positive cells in H9c2 cardiomyocytes, which was prevented by ACh. The

salutary effects of ACh were blocked by epidermal growth factor receptor (EGFR)/muscarinic

ACh receptor-2 (M2AChR) siRNA, indicating that EGFR/M2AChR pathway may be involved in

the benefits of ACh in cardiomyocytes. (2) In endothelial cells, ACh reduced H/R-induced ER

stress, cell apoptosis as well as ER ultrastructural changes. M3AChR/AMP-activated protein

kinase (AMPK) siRNA diminished the attenuation of GRP78, CHOP and cleaved-caspase-12

expression elicited by ACh. ACh-induced endothelial protection may be attributed to the up-

regulation of M3AChR activated AMPK signaling.

Conclusion: ACh inhibited ER stress and protected cardiomyocytes and endothelial cells through

muscarinic receptor-mediated signaling cascades in inflammatory and ischemic injury, suggesting

that inhibition of ER stress may be a novel mechanism underlying ACh-induced cardiovascular

protection.

ischemic injury.

Supported by: grant from National Natural Science Foundation of China (Major International Joint

Research Project, No. 81120108002; General Project, No. 81473203), Specialized Research Fund

for the Doctoral Program of Higher Education (No. 20130201130008).

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ROLE OF AMP-ACTIVATED PROTEIN KINASE (AMPK) IN VASCULAR

ENDOTHELIAL PROTECTION A. Shamsi, J. Mason

Vascular Sciences Division, NHLI Cardiovascular Research, Hammersmith Hospital, London,

United Kingdom

Background: Adenosine monophosphate-activated protein kinase (AMPK), although known for

its role in regulating cellular metabolism, has recently emerged as an important kinase involved in

vascular endothelial protection. We noted it to have similar actions as those of MnSOD, HO-1 and

DAF, genes that protect the endothelium from inflammatory and oxidative stress, and so we

investigated whether AMPK’s cytoprotective activity includes the induction of these genes and

explored the signalling pathways that may be involved.

Methods: Human umbilical vein endothelial cells first underwent a flow perfusion assay. They

were then treated with AICAR (an AMPK activator), for 24 hours, AMPK adenovirus (Ad CA-

AMPK) for 18 hours or the combination of atorvastatin and rapamycin for 2 hours and either

immunoblotted for various proteins or analysed via flow cytometry. Transcription factor CREB

was silenced using siRNA.

Results: In this study we showed that oscillatory shear stress may be responsible for down-

regulating levels of phospho-AMPK and HO-1. Cells treated with AICAR had a significant

increase in MnSOD, HO-1 and DAF protein expression. Ad CA-AMPK was shown to deliver

active forms of AMPK into the cells and infection of this adenovirus also up-regulated the levels

of MnSOD, HO-1 and DAF. We also showed that AMPK activates CREB. Our results suggest

that depletion of CREB with siRNA reduces MnSOD protein induction by Ad CA-AMPK.

Conclusion: We showed that AMPK activation induces the cytoprotective genes MnSOD, HO-1

and for the first time, DAF. We have also suggested that CREB may be involved in the pathway

for AMPK-dependent induction of MnSOD and that AMPK activation may be a future therapy

target.

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280

THE PROTECTIVE EFFECTS OF CATECHIN ON PALMITIC ACID -INDUCED

CYTOTOXICITY IN MOUSE BRAIN ENDOTHELIAL CELL K.L. Wong1,2,3,4, C.W. Cheung2, C.Z. Chao3,4, T.H. Su1,5, Y.M. Leung5 1. Department of Anesthesiology, China Medical University & Hospital, Taichung, Taiwan

2. Department of Anesthesiology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong

3. Shandong University, Qilu Hospital-Nanshan Hospital, Shandong, China

4. Department of Anesthesiology, Taishan Medical University, Shandong, China

5. Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan

Aims: The approximate prevalence of the metabolic syndrome (MS) in patients with coronary heart

disease (CAD) is 50%, with a prevalence of 37% in patients with premature CAD. Effective

prevention or treatment of MS significantly reduces the risk for developing serious complications.

Palmitic acid (PA) is a saturated fatty acid, when being excessive, is a significant risk factor for

development of MS or cardiovascular accident. Lipotoxicity in endothelial cells (EC) has been

well documented but how PA affects EC Ca2+-signaling and other functions remain largely

unexplored. Catechin has been implicated in benefiting almost every organ system such as

cardioprotective and anti-obesity; and also beneficial for blood vessel health. This study aims to

investigate the lipotoxic alteration of mouse brain endothelial cell line (bEND.3 cells) function

mediated by PA; and how PA modulates EC ion channels, and also to assess the potential

protective effects of catechin.

Methods: Cell apoptosis assessed by TUNEL-Assay. Cytosolic Ca2+ in bEND was measured with

Fura-2 method. Mitochondria membrane potential (MMP) measured by MMP-Assay Kit. Cell

viability was measured By MTT-Assay. The p < 0.05 were considered significant (ANOVA).

Results: Exposure of bEND to PA (300 micromolar) for 48 h resulted in apoptosis. PA (100, 300

micromolar) increased expression of CHOP but not phosphorylated eIF2-alpha. PA (300

micromolar) pretreatment diminished (Ca2+agonist) ATP-triggered Ca2+ release and Ca2+ influx.

300 micromolar PA pretreatment diminished (SR Ca2+-pump blocker) CPA-triggered Ca2+

release and Ca2+ influx. Thus PA at this high concentration reduced the size of Ca2+ pool. PA at

100 micromolar, however, did not reduce CPA-induced Ca2+ release but suppressed Ca2+ influx.

Thus PA at this concentration inhibits store-operated Ca2+ entry. PA-induced cell death was

significantly alleviated by co-treatment of bEND with catechin (300 micromolar).

Conclusion: Cell death was apoptotic and related to endoplasmic reticulum(ER) stress and

cytosolic Ca2+ elevation. Co-treatment of bEND with catechin (300 µM) significantly

prevented PA-induced cell death.

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281

INTERFERON GAMMA SIGNALLING IN ATHEROSCLEROSIS: PRO-

ATHEROGENIC ACTIONS AND THERAPEUTIC APPROACHES T.S. Davies1, H. Gallagher1, F. Jaafar1, J.W. Moss1, T.R. Hughes2, D.P. Ramji1

1. School of Biosciences, Cardiff University, Cardiff, UK

2. School of Medicine, Cardiff University, Cardiff, UK

Objectives: To investigate the mechanisms underlying the effects of interferon-gamma on

macrophages in atherosclerosis and how therapeutic agents attenuate the actions of this pro-

inflammatory cytokine.

Background: Atherosclerosis is an inflammatory disease of medium and large arteries regulated

by cytokines. The pro-atherogenic cytokine interferon-gamma (IFN-gamma) plays a pivotal role

in all stages of the disease and hence represents a promising therapeutic target. The purpose of this

study was to investigate how IFN-gamma modulates macrophage function and properties in this

disease along with the mechanisms underlying the inhibition of its actions by therapeutic agents.

Methods: The studies used a combination of macrophage cell lines and primary cultures together

with analysis of gene expression and signal transduction pathways, RNA interference assays and

biochemical approaches.

Results: IFN-gamma induced macrophage foam cell formation and the expression of several pro-

inflammatory genes, such as monocyte chemotactic protein-1 and intercellular adhesion molecule-

1, and microRNAs. The extracellular signal-regulated kinase (ERK) pathway played a pivotal role

in the action of the cytokine on the promotion of modified lipoprotein uptake by macrophages and

the regulation of expression of pro-atherogenic genes. ERK modulated the phosphorylation-

mediated activation of signal transducer and activator of transcription-1 (STAT1), a key

transcription factor in IFN-gamma signalling. The pro-atherogenic actions of IFN-gamma were

attenuated by statins, activators of anti-atherogenic nuclear receptors, and nutraceuticals such as

dihomo-gamma-linolenic acid. The mechanisms underlying the inhibitory actions of such agents

along with the role of the ERK:STAT1 axis in the promotion of atherosclerotic in vivo are currently

being investigated.

Conclusions: The studies provide key mechanistic insights into the pro-atherogenic actions of IFN-

gamma and the effects of therapeutic agents on signalling by this cytokine.

Funding: British Heart Foundation

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282

MICRORNA-15/16 PROMOTES SMOOTH MUSCLE CONTRACTILE PHENOTYPE

AND ATTENUATES VASCULAR NEOINTIMA FORMATION BY TARGETING YES-

ASSOCIATED PROTEIN YAP F. Xu1,2, A. Ahmed1, X. Kang1,2, G. Hu1, W. Zhang2, J. Zhou1

1. Department of Pharmacology & Toxicology, Medical College of Georgia, Georgia Regents

University, Augusta, GA, USA

2. Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University,

Nanchang, China

Objectives: To investigate the functional role of the microRNA (miR)-15/16 in vascular smooth

muscle phenotypic modulation and its underlying mechanism.

Background: In response to vascular injury, vascular smooth muscle cells (VSMCs) undergo

phenotypic modulation from contractile phenotype to synthetic phenotype that is characterized

with the elevation of VSMC proliferation and migration while reduction of muscle contractile

genes. This phenotypic switching leads to neointima formation that can cause many occlusive

vascular diseases such as restenosis. Previous studies have shown that miRs encoded by the miR-

15/16 clusters act as tumor suppressors, but the functional role of miR-15/16 in VSMCs is

unknown.

Methods and Results: By using quantitative reverse-transcription polymerase chain reaction, we

found that miR-15/16 is the one of most abundant microRNAs expressed in contractile VSMCs.

However, when contractile VSMCs convert to synthetic phenotype in vitro and in vivo miR-15/16

expression is significantly reduced. By loss-of-function assays, knocking-down endogenous miR-

15/16 in VSMCs attenuates smooth muscle gene expression but promotes VSMC proliferation and

migration. Conversely, over-expression of miR-15/16 promotes smooth muscle contractile gene

expression while attenuating SMC migration and proliferation. Consistent with this, over-

expression of miR-15/16 in a rat carotid balloon injury model markedly attenuates injury-induced

smooth muscle dedifferentiation and neointima formation. Mechanistically, we identified the

potent oncoprotein yes-associated protein YAP as a downstream target of miR-15b/16 in human

VSMCs. Reporter assays validated that miR-15/16 targets YAP 3'-untranslated region through an

evolutionarily conserved binding site. Furthermore, over-expression of miR-15/16 significantly

represses YAP expression, whereas conversely, depletion of endogenous miR-15/16 results in up-

regulation of YAP expression.

Conclusions: These results indicate that miR-15/16 plays a critical role in smooth muscle

phenotypic modulation by targeting YAP. Promoting expression of miR-15/16 would be a

potential therapeutic approach for treatment of proliferative vascular diseases.

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283

IS THERE A RELATIONSHIP BETWEEN ADVANCED GLYCATION END-

PRODUCTS AND SOLUBLE RECEPTORS OF ADVANCED GLYCATION END-

PRODUCTS WITH THE ETIOLOGY AND SEVERITY OF CONGESTIVE HEART

FAILURE? A.F. Zand Parsa, S. Nejati, A. Esteghamati

Tehran University of Medical Sciences, Tehran, Iran

Background: Advanced glycation end-products (AGEs) and the soluble receptor for advanced

glycation end products (sRAGEs) came up with the recent researches regarding new biomarkers

for the diagnosis of congestive heart failure (CHF). Although it has been known that AGEs and

sRAGEs have a role in the pathogenesis of CHF, information regarding their role and their

pathogenetic mechanism is very limited. The aim of this study was to find any relationship between

AGEs and sRAGEs with the etiology and severity of CHF.

Methods and Material: This study was a prospective cross sectional study that enrolled 85 patients

with chronic CHF. Measurement of left ventricle ejection fraction (LVEF) was done by

echocardiography. Blood samples were collected for measuring AGEs and sRAGEs just before or

after echocardiography assessment (in the same session). Measurement of AGEs, sRAGEs and

NT-pro BNP were done by ELISA method. The relationship between AGEs and sRAGEs with the

severity and as well as the etiology of CHF were evaluated via SPSS-15.

Results: Of 85 patients 48 (56.5%) were male; Mean±SD of their ages was 55.8±13.4 years old

(ranges from 27 to 84 years). Correlation coefficient between LVEF and sRAGEs was 0.196

(P=0.072) and between LVEF and AGES was 0.269 (P=0.013). Mean of sRAGEs in the patients

with and without ischemic etiology was 3.4±2.2 microgram/ml and 2.8±4.2 microgram/ml,

respectively (P=0.141). Mean of AGES in the patients with and without ischemic etiology was

16.8±9.8 microgram/ml and 11.6±7.3 microgram/ml, respectively (P=0.141). Although there was

trend in favor of ischemic heart failure, the difference between two groups was not statistically

significant.

Conclusion: According to this study the rate of AGES and sRAGEs could be helpful in the

diagnosis and assessment of severity of CHF and may be used for etiologic differentiation of heart

failure syndrome.

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THE ROLE OF SIRT6 IN ENDOTHELIAL CELL SENESCENCE AND

CYTOPROTECTION J.D. Erusalimsky1, A.K. Uryga2

1. Cardiff Metropolitan University, Cardiff, UK

2. University of Cambridge, Cambridge, UK

The wear and tear processes that contribute to human ageing are being increasingly implicated in

the development of cardiovascular pathologies. One such process is telomere damage, which leads

to the onset of cellular senescence. Although the occurrence of senescence in the vascular

endothelium is now clearly established (reviewed in Erusalimsky, J. Appl. Physiol. 2009;106:326),

the mechanisms of its regulation have not been extensively investigated. SIRT6 is a member of a

family of NAD-dependent protein deacylases known to influence metabolism, stress tolerance and

ageing. SIRT6 participates in DNA repair, telomere maintenance, and transcriptional repression

of genes that regulate glucose homeostasis and inflammation. Since these processes may be

relevant to cardiovascular pathologies, we are investigating the function of SIRT6 in endothelial

cells (Cardus et al, Cardiovascular Res. 2013;97:571). In this presentation I will show evidence

that SIRT6 is present in mature endothelial cells and that its levels decrease upon senescence. I

will also show that knock down of SIRT6 by RNA interference increases global DNA damage as

well as telomere damage, resulting in the activation of a DNA damage response, which leads to

the inhibition of cell proliferation and the establishment of a senescent phenotype. These effects

are accompanied by an increase in the expression of pro-inflammatory and pro-thrombotic

markers, by a reduction in endothelial nitric oxide synthase expression, and by impairment in the

formation of capillary-like networks. Our findings highlight the role of SIRT6 as an important

regulator of endothelial cell homeostatic functions and suggest that its modulation may affect the

evolution of vascular ageing.

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SYNCOPE AND SUDDEN DEATH: RISK ASSESSMENT AND MANAGEMENT

285

INCIDENCE AND ELECTROGRAM CHARACTERISTICS OF NON-SUSTAINED

VENTRICULAR FIBRILLATION IN PATIENTS WITH PRIMARY ELECTRICAL

DISORDERS K.J. Choi1, W.S. Lee1, J. Kim1, C.H. Kwon1, J.H. Choi1, U. Jo1, Y.R. Kim1, G.B. Nam1, Y.H.

Kim1, J.H. Zo2

1. Asan Medical Center, Ulsan University, Seoul, Korea

2. Seoul Municipal Boramae Hospital, Seoul, Korea

Background: Implantable cardioverter defibrillator (ICD) is frequently indicated in high risk

patients with primary electrical disorders (Brugada syndrome [BrS], early repolarization syndrome

[ERS], and idiopathic ventricular fibrillation [IVF]). Some patients present with ventricular

fibrillation (VF) that terminates spontaneously. But limited information is available on non-

sustained VF.

Objectives: The aim of the present study was to compare non-sustained VF and VF terminated by

electrical shock and to investigate the difference of fluctuation in ventricular cycle length (CL)

that could predict the self-termination of arrhythmia before electrical shock delivery.

Methods: We enrolled consecutive 27 patients (41.5+¾13.2 years; 22 males) with primary

electrical disorders (BrS 16, ERS 7, IVF 4 patients) who experienced VF on ICD interrogation

between April, 1996 and April, 2014. A total of 228 episodes were reviewed by two independent

cardiac electrophysiologists.

Results: (1) Of 228 episodes, 193 (84.6%), 35 (15.4%) episodes were VF terminated by electrical

shock and non-sustained VF, respectively. (2) Mean VFCL in non-sustained VF was longer than

in VF terminated by electrical shock (193+¾35 vs. 179+¾28 ms)(P=0.036). (3) In each episode,

VFCL became longer or did not change in non-sustained VF (187¡¾31 vs. 196¡¾38 ms)(first vs.

last CL)(P=0.276) in contrast with progressively shorter VFCL in VF terminated by electrical

shock (180+¾25 vs. 160+¾29)(first vs. last VFCL before electrical shock)(P<0.001).

Conclusion: Non-sustained VF in primary electrical disorders was not infrequent. VFCL was

longer and progressively increased or did not change in non-sustained VF compared with VF

terminated by electrical shock. Whether ICD programming reflecting this characteristic shortening

of VFCL could decrease frequency of ICD shock awaits further study.

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286

EARLY EMERGENCY CALLS BEFORE PATIENT COLLAPSE AND SURVIVAL

FROM OUT-OF-HOSPITAL CARDIAC ARREST H. Inaba1, Y. Takei2, T. Nishi1, T. Kamikura1, H. Iwasaki1, A. Funada1


2. Hiroshima International University, Higashi-hiroshima, Hiroshima, Japan

Aim: Some out-of-hospital cardiac arrests (OHCAs) are witnessed after emergency calls. This

study aimed to confirm the benefit of early emergency calls before patient collapse on survival

after OHCAs witnessed by bystanders and/or emergency medical technicians (EMTs).

Methods: We analysed 278,310 witnessed OHCAs [EMT-witnessed cases (n = 54,172), bystander-

witnessed cases (n = 224,138)] without pre-hospital physician involvement from all Japanese

OHCA data prospectively collected between 2006 and 2012. The data were analysed for the

correlation between neurologically favourable 1-month survival and the time interval between the

emergency call and patient collapse.

Results: When emergency calls were placed earlier before patient collapse, the proportion of EMT-

witnessed cases and survival rate after OHCAs witnessed by bystanders and EMTs were higher.

When analysed only for bystander-witnessed cases, for earlier emergency calls placed before

patient collapse, survival rate and incidences of bystander cardiopulmonary resuscitation (CPR)

and dispatcher-assisted CPR decreased: 2.9%, 33.6% and 24.4%, respectively, for emergency calls

placed >6 min before collapse and 5.5%, 48.8% and 48.5%, respectively, for those placed 1–2 min

after collapse. Multivariable logistic regression showed that short call-to-collapse interval

(adjusted odds ratio; 95% confidence interval) (0.92; 0.90–0.94) and EMT response time after

collapse (0.84; 0.82–0.86) were associated with survival after bystander-witnessed OHCAs with

emergency calls before collapse.

Conclusion: Early emergency calls before patient collapse efficiently increase the proportion of

EMT-witnessed cases and promotes survival after OHCAs witnessed by EMTs and bystanders.

However, early emergency call before collapse may interfere with the detection and recognition

of cardiac arrest by dispatchers and may worsen the outcome when the patient’s condition

deteriorates to cardiac arrest before EMT arrival.

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287

COMPONENT ANALYSIS FOR EFFECTIVENESS OF VENTILATIONS AND

COMPRESSIONS IN BYSTANDER CARDIOPULMONARY RESUSCITATION H. Inaba1, T. Kamikura1, H. Iwasaki1, Y. Takei2, T. Maeda1


2. Hiroshima International University, Higashi-hiroshima, Hiroshima, Japan

Aim: To determine the effectiveness of ventilations and compressions in bystander

cardiopulmonary resuscitation (BCPR).

Methods: From out-of-hospital cardiac arrest (OHCA) data prospectively collected from 2005 to

2011 in Japan, we extracted data for 210,134 bystander-witnessed OHCAs with complete datasets

but no prehospital involvement of physician [no BCPR, 115,733; ventilation-only, 2,093;

compression-only, 61,075; and conventional (compressions + ventilations) BCPR, 31,233] and

performed univariable component analyses of ventilation and compression for 1-month

neurologically favourable using simple multinominal and multivariable logistic regression

analysis.

Results: The rate of survival in the no BCPR, ventilation-only, compression-only and conventional

group was 2.8%, 3.9%, 4.5% and 5.0%, respectively. The unadjusted OR (95% CI) for survival

after dividing BCPR into ventilation and compression components were 1.13 (1.06–1.20) and 1.64

(1.56–1.72), respectively. When adjusted by other factors known to be associated with survival,

the adjusted OR (95% CI) were 1.19 (1.11-1.27) and 1.60 (1.51-1.69), respectively. The adjusted

OR of ventilation component was high in the OHCA subgroup of non-cardiac etiology (1.38; 1.19-

1.59) and very high in the pediatric OHCA subgroup (1.56; 1.13-2.15).

Conclusions: Ventilation is a significant component of BCPR, but alone is less effective than

compression in improving neurologically favourable survival after OHCAs.

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288

EARLY HEMODYNAMIC CHANGES OF TILT TABLE TESTING PREDICTS

NEUROCARDIOGENIC RESPONSE IN AFRICAN AMERICAN POPULATION D. Ho, M. Ghods, S. Kumar, N. Warrier, H. Ilias Basha, J. Kassotis

SUNY Downstate, New York, NY, USA

Background: Head up tilt table test (HUTT) is both time consuming and has an associated

morbidity. Hemodynamic changes that occur during the early phase of HUTT may allow for

prediction of neurocardiogenic syncope, without vasoactive stimulation thus, reducing protocol

time and any associated morbidity.

Methods: 119 consecutive African Americans (AA) (57±19, male 44%) underwent a HUTT for

evaluation of syncope of unknown etiology (8/2011-12/2013). A positive response was defined as

the development of symptoms linked with an SBP < 90 mm Hg, HR < 50 beats/min, or sinus arrest

> 3 seconds. Hemodynamic variables during the passive phase of HUTT were analyzed, and results

were then classified into groups (positive vs. negative), as a function of various predictors (age,

early changes in HR, SBP and DBP) and a decision tree was generated.

Results: 62 subjects (52%) had positive HUTT and 57 (48%) had negative HUTT. Early changes

in HR from baseline (up to 9 minutes) did not predict HUTT response. Early changes in BP

variables from baseline significantly predicted HUTT response (p<0.05). There was significant

interaction between age and BP; SBP for age>60 but DBP for age<60. An algorithm (Fig 1) based

on age and BP had a positive predictive and negative predictive value of 68 and 93 %, respectively,

with an accuracy of 80%.

Conclusion: A novel algorithm using age and BP allows for the early prediction of HUTT results

without need for vasoactive stimulation which allows for rapid diagnosis, lower morbidity and a

reduction in cost.

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289

QUANTITATIVE SUDOMOTOR AXON REFLEX TEST (QSART) STUDY IN

POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME (POTS) C. Ashangari, A. Suleman

The Heartbeat Clinic -Department of Cardiology, Mckinney, TX, USA

Objectives: The aim of this study is to determine the association of QSART deformities in Postural

Orthostatic Tachycardia Syndrome (POTS) patients.

Background: The Postural Orthostatic Tachycardia Syndrome (POTS) affects primarily young

women. POTS is a form of dysautonomia that is estimated to impact between 1,000,000 and

3,000,000 Americans, and millions more around the world. Quantitative Sudomotor axon reflex

test (QSART) is used to evaluate postganglionic sympathetic cholinergic Sudomotor function by

measuring the axon-reflex mediated sweat response over time.

Methods: 192 patients were selected randomly from our clinic with POTS who underwent QSART

test .Patients Sudomotor Evaluation results were reviewed from electronic medical records and

performed data analysis

Results: Out of 192 patients, 181 patients are female (94%, n=181, age 33.78±11.46), 11 patients

are male (6%, n=11, age 27.88±9.29).QSART was abnormal in 129/192(67%) patients in which

83 patients had excessive sweating, 46 patients had Loss of sweating. 62/192(32%) patients had

normal QSART.

Conclusion: Our research results demonstrated that POTS patients have a higher percentage of

QSART abnormalities (67%).

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290

WHAT’S COMMON IS COMMON! P.A. Patel, B. Gersh

Mayo Clinic, Rochester, MN, USA

Objectives/Background: Syncope is a common health problem encountered by internists and

cardiologists. Here we describe a case of a young woman with multiple syncopal episodes.

Description: 33 year old lady with PMH of syncopal episodes and hypothyroidism was admitted

to CCU after experiencing presyncope and hypotension during an EEG session as part of outpatient

syncope evaluation. In the previous 6 months, she had an unremarkable but an exhaustive cardiac

and neurologic workup including Holter monitoring, MRI/MRA of brain, EEG, thermoregulatory

sweat test, quantitative axon reflex sweat test and a 10 minute 70° angle tilt table study. History

taking revealed that her syncopal episodes would generally occur after prolonged standing with a

prodrome of presyncope, tunneling vision and palpitations followed by loss of consciousness for

~30 seconds and complete recovery. A 70° angle tilt table study was abnormal after 45 minutes as

patient had syncope associated with BP 84/71 and HR 49 suggesting vasovagal syncope. She was

discharged with Midodrine and compression stockings.

Results/Discussion: It’s important to clinically differentiate syncope from vertigo or seizure before

embarking on a workup. Important clues from history like prodrome, provocative factors,

associated symptoms, pre-existing medical conditions etc. and from physical exam like orthostatic

hypotension, cardiac murmurs etc. can often point to an etiology. Three main etiologies of syncope

are reflex/neurally mediated (including vasovagal), orthostatic hypotension and cardiac with the

former two being more common and cardiac syncope being the most worrisome.

Conclusion: A good history and physical are essential for a cost-effective yet safe evaluation of

syncope.

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291

CURIOSYNCOPY V.O. Obi, N. Isber, D.A. Bloomfield

Department of Medicine, Richmond University Medical Center Staten Island, New York USA

Although the usual causes of syncope such as vaso-vagal, orthostatic and obstructive types are

well recognized, the associated symptoms of unusual causes may be confusing and the

management less obvious.

We present some rare types of syncope managed in our facility, where the cause was not

immediately apparent.

Swallow (Bagel) syncope. A patient presented with several episodes syncope and a normal

examination. Further history indicated a relationship to meals and EKG monitoring revealed

paroxysmal AV block in which reduced cerebral blood flow corresponded to eating solid foods.

Subclavian steal syncope.

A patient complained of pain when raising the left arm. There was also blurring of vision, vertigo,

and episodes of syncope. Arm muscle and joint examination was normal but blood pressure was

30mmHg lower in the left arm. Arteriography demonstrated subclavian steal diminishing cerebral

blood flow during arm raising.

Systemic mastocytosis syncope

A patient presenting with multiple syncope episodes, each associated with flushing, palpitation,

itching and hypotension. The history suggested histamine reaction episodes. Examination was

normal but bone marrow biopsy revealed increased mast cells.

Pan-dysautonomia neuropathy.

A patient was admitted with recurrent syncope after standing, associated with dry mouth,

decreased sweating and constipation. Examination was normal but Tilt-table testing showed

immediate blood pressure drop of 70mmHg.

Laugh syncope

A barber presented with shoulder pain after falling at work. Only bruising was found but further

questioning revealed that immediately before falling unconscious, he had broken out in very hearty

laughter at a joke told him by a customer.

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ARRHYTHMIAS: DIAGNOSIS AND TREATMENT – BASIC AND CLINICAL

292

PRO-ARRHYTHMIC EFFECTS OF CALMODULIN KINASE II (CAMKII) IN

TIMOTHY SYNDROME ARISING FROM A NEW CACNA1C MUTATION J.Y Bai1, K.Q. Wang1, H.G. Zhang2

1. School of Computer Science and Technology, Harbin Institute Technology, Harbin,

Heilongjiang, China

2. School of Physics and Astronomy, University of Manchester, Manchester, UK

Background: Timothy syndrome (TS) is a disease of excessive cellular Ca2+ entry and life-

threatening arrhythmias caused by a mutation in the primary cardiac L-type Ca2+ channel.

Recently, a novel TS mutation (G1911R) was identified. While its genetic basis has become well-

understood, the cellular mechanisms (especially the role of CaMKII) by which the mutation

translates to arrhythmia susceptibility remain unclear.

Objectives: This study aims at exploring mechanisms by which CaMKII modulates

arrhythmogenesis and identifying potential targeted sites of antiarrhythmic therapy in TS.

Methods: A human ventricular cell model incorporated with a CaMKII activation module was

used. Effects of CaMKII on L-type Ca2+ channel, RyR2 receptor and SERCA2a were considered.

Parameters in the equations of ICaL were modified to incorporate experimental data on G1911R

mutation.

Results: Our results indicate that: 1) In intracellular ionic simulations, TS myocytes had excessive

ICaL(155%), more activated CaMKII(10-fold), higher SR Ca2+ load (133%), larger amplitude

Ca2+ transients(183%), and augmented frequency of Ca2+ waves(300%). The large SR Ca2+

release in TS had a profound effect on the kinetics of ICaL, increasing the rate of inactivation to a

high level resulted from larger fraction of CaMKII activation. 2) In action potential simulations,

CaMKII-dependent ICaL facilitation contributes to excessive action potential prolongation(from

413.6 to 1133.9 ms) which favors the generation of early afterdepolarizations (EADs); CaMKII-

dependent SR overload results in SR Ca2+ leak for triggering delayed afterdepolarizations

(DADs). 3) In CaMKII inhibition simulations, CaMKII inhibition reversed an increase in

intracellular Ca2+, normalized action potential and prevented afterdepolarizations.

Conclusions: TS-mediated Ca2+ influx is an upstream initiating event for arrhythmia phenotypes

that are ultimately dependent on CaMKII activation. Thus, ICaL block in combination with partial

CaMKII inhibition may be potentially a new therapeutic target to treat TS patients.

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293

GASTROINTESTINAL DISTURBANCES IN POSTURAL ORTHOSTATIC

TACHYCARDIA SYNDROME (POTS) C. Ashangari, A. Suleman

The Heartbeat Clinic -Department of Cardiology, Dallas, TX, USA

Objectives: The aim of this study is to determine the Gastrointestinal disturbances in Postural

Orthostatic Tachycardia Syndrome (POTS) patients.



3,000,000 Americans, and millions more around the world. POTS is a form of orthostatic

intolerance that is associated with many Gastrointestinal disturbances.

Methods: 249 patients are referred to our clinic from January to November with POTS. Reviewed

the medical records of 249 POTS patients and gastrointestinal symptoms

Results: Out of 249 patients, 226 patients are female (90.76%; average age 32.69), 23 patients are

male (9.24%; average age 27.91). Out of 249 patients 189 patients (76%) had vomiting or nausea,

150 patients (60%) had irritable bowel syndrome ,128 patients (51%) had bloating, 125 patients

(50%) had constipation , 80 patients (32%) had abdominal pain , 56 patients (22 %) had delayed

gastric emptying, 24 patients (10%) had lactose intolerance, 8 patients (3 %) had

Gastroesophageal reflux disease, 5 patients (2 %) had Iron deficiency anemia, 6 patients (2 %) had

Peptic ulcer disease, 4 patients (2 %) had Celiac Disease.

Conclusion: Patients with POTS have a very high prevalence of gastrointestinal symptoms

however the majority of abnormalities appear to be motility related. Motility testing should be

performed in POTS patients. The diagnostic yield of endoscopic procedures appears to be low.

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294

VITAMIN B12 DEFICIENCY IN POSTURAL ORTHOSTATIC TACHYCARDIA

SYNDROME (POTS) C. Ashangari, A. Suleman

The Heartbeat Clinic -Department of Cardiology, Mckinney, TX, USA

Objective: The aim of this study is to investigate the association between vitamin B12 levels and

Postural orthostatic tachycardia syndrome (POTS).



3,000,000 Americans, and millions more around the world. We frequently find vitamin B12

deficiency in patients who present with POTS. Vitamin B12 is involved in the production of

adrenaline from noradrenaline. It is the cofactor involved in catecholamine degradation.

Methods: 155 patients were selected randomly from our clinic with POTS. Patients Vitamin b12

levels charts were reviewed from electronic medical records, Vitamin b12 deficiency status was

defined as serum level <200 pg/mL.

Results: Out of 155 patients, 146 patients are female (94%, n=146, age 33.68±7.26), 9 patients are

male (6% ,n=9 ,age 24.73±4.39). 89/155(57%) patients had Vitamin B12 serum level <200 pg/mL,

66(43%) patients had Vitamin B12 serum level >200 pg/mL.

Conclusion: Our research results demonstrated that Postural Orthostatic Tachycardia Syndrome

(POTS) patients have significantly lower vitamin B12 levels (57% have Vitamin B12 deficiency

serum level <200 pg/mL).

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295

AN UNUSUAL TYPE OF SHORT V-V TAHCYCARDIA A. Almomani, A. Abualsuad, H. Paydak, W. Maskoun

University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System,

Little Rock, AR, USA

Case and Discussion: 42 year-old male with coronary artery disease and ischemic cardiomyopathy

who underwent right-sided single chamber Implantable Cardioverter-Defibrillator placement by

cardiothoracic surgery in August 2012. On device interrogation, he was found to have multiple

asymptomatic tachycardia episodes. The device intracardiac electrograms were reviewed and

showed short V-V tachycardia, which was interpreted as non-sustained ventricular tachycardia

(NSVT). 12-lead EKG and Chest X-ray were not remarkable. However, when we compared the

ventricular signal during the short V-V interval seen in device interrogation to the ventricular

signal during sinus rhythm, they looked similar except for further separation of the two

components of the ventricular signal during the short V-V interval on the EMG.

Pacing the ICD lead at the maximum output as part of work up to evaluate the possible diagnosis,

which resulted in atrial capture only and morphology of the P wave was consistent with left atrial

capture. This finding raised the possibility of lead misplacement. Chest x-ray with lateral

projection was obtained and demonstrated ICD lead misplacement into the coronary sinus (CS) or

left atrium. Echocardiography was done and confirmed lead misplacement in the CS and not in the

left atrium. The two components were basically both near field A and V (not far field) and the

episodes reported as NSVT were actually atrial tachycardia episodes with further separation of the

A and V due to the AV nodal delay during the tachycardia. The fact that the tachycardia episodes

terminated with V each time, rules out ventricular tachycardia with one to one retrograde

conduction.

Patient was seen during follow up at 1 and 6 months, and ICD interrogation showed normal

sensing, pacing and no more episodes of short V-V tachycardia.

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296

EFFECTS OF ANESTHESIA ON INDUCIBILITY DURING PEDIATRIC

ELECTROPHYSIOLOGY STUDIES M. Gupta, A. Lawerence, C. Snyder

Rainbow Babies and Children's, Case Western Reserve University School of Medicine,

Cleveland, OH, USA

Background and introduction: Anesthesia has become an important part of pediatric

electrophysiology studies (PEP). The purpose was to determine, (1) the prevalence of

supraventricular tachycardia (SVT) and sinus tachycardia (Stach) during anesthesia induction, and

(2) lack of inducibility of SVT during PEP under anesthesia.

Methods: IRB approved, retrospective review of PEP (1/99-1/14). Inclusion criteria: Less than 21

years, documented SVT prior to PEP, anesthesia. Data review: demographics, EP and anesthesia

records. Two groups identified, Intravenous (IV) and inhalational anesthesia (I). Induction of SVT

and Stach prior to initiating EP study was recorded as was failure to induce SVT during PEP.

Results: Inclusion criteria was met by 378 patients, 57% males, median age 14 years. IV anesthesia

in 72% . During induction, only 1 patient from IV group developed SVT, (WPW patient), 10% of

patients developed Stach and patients with WPW are twice at risk of developing Stach (16.19%

vs. 8.06%; p = 0.02). Stach was seen more commonly with I induction (59% Vs 41%; p < 0.0001).

The most common drug for I was sevoflurane ( 89%); and no differences were identified between

drugs. Failure to induce SVT during PEP was 13 % and no differences seen between groups.

Conclusion: Route of anesthesia induction, inhaled or intravenous do not increase the risk of

developing SVT. Sinus tachycardia is a common occurrence, and failure to induce SVT was not

affected route of anesthesia.

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297

RELATIONSHIP OF BODY MASS INDEX (BMI) AND POSTURAL ORTHOSTATIC

TACHYCARDIA SYNDROME (POTS) C. Ashangari, A. Suleman

The Heartbeat Clinic -Department of Cardiology, McKinney, TX, USA

Objective: The purpose of this study is to determine the relationship of body mass index (BMI)

and Postural Orthostatic Tachycardia Syndrome (POTS).



3,000,000 Americans, and millions more around the world. Body mass index (BMI) is a measure

of relative size based on the mass and height of an individual.

Method: 169 patients were selected randomly from our clinic with POTS; Patients BMI charts

were reviewed from electronic medical records. Patients were categorized as normal weight (BMI

18.5 to 24.9 kg/m2), overweight (BMI 25.0 to 29.9 kg/m2) or obese (BMI ≥30.0 kg/m2).

Results: Out of 169 patients (n=169), 97% are females (n=164; age 30.88±9.36), 3% are males

(n=5; age 25.93±6.19), 51 Patients (30%) have normal weight (20.37±3.29kg/m2), 86 Patients

(51%) have overweight (25.46±3.10 kg/m2), 32 Patients (19%) have Obesity (30.11±6.3 kg/m2).

Conclusion: Our results, for the first time, demonstrated the POTS and BMI relationship. In POTS

patients higher percentage (51%) have overweight BMI (25.0 to 29.9 kg/m2), more than half of

POTS patients (70%) have BMI (≥25.0 kg/m2).

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298

RECURRENT VENTRICULAR TACHYCARDIA IN A METHADONE DEPENDENT

PATIENT WITH NON-COMPACTION CARDIOMYOPATHY Y.E. Alansari, R.C. Hendel

University of Miami Miller School of Medicine, Miami, FL, USA

Background: Methadone is a commonly used drug for opioid dependence and chronic pain.

Cardiac side effects, especially QT interval prolongation and ventricular arrhythmias have recently

become a concern, even though it rarely causes ventricular arrhythmias.

Case Report: In this report, we describe a case report of a 41 year-old female on chronic methadone

who used cocaine 3 days before a syncopal episode, which was due to polymorphic ventricular

tachycardia. The patient was also noted to have a non-compaction cardiomyopathy. The patient

was treated with an amiodarone infusion, tapered off the methadone and underwent VT ablation.

However, the ventricular tachycardia continued to be easily inducible and a dual chamber

implantable cardioverter-defibrillator (ICD) was placed. This report highlights the interaction of

methadone and structural heart disease and the role each plays in complex ventricular ectopy.

Discussion: Even though methadone can cause QT interval prolongation, it is rarely the sole cause

of ventricular arrhythmia and other risk factor are usually associated with the ventricular

arrhythmia in patients on a steady dose of methadone, such as hypokalemia, hypomagnesaemia,

structural heart disease, administration of other drug that can cause QT interval prolongation like

including cocaine, haloperidol, erythromycin.

Conclusion: Methadone is known to cause acquired QT interval prolongation but it is rarely a sole

cause of ventricular arrhythmias. Around 50% of patients with non-compaction cardiomyopathy

developed ventricular arrhythmias, usually in the setting of other risk factors. Cocaine,

hypokalemia, hypomagnesemia and non-compaction cardiomyopathy all contributed in

ventricular arrhythmias in this patient with chronic methadone use and QT interval prolongation.

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299

WIDE COMPLEX TACHYCARDIA IN A YOUNG PATIENT

A. Abualsuod1, A.A. Almomani1, H. Paydak1, D. Abhishek2, W. Maskoun1

1. University or Arkansas for Medical Sciences, Little Rock, AR, USA

2. Mayo Clinic, Rochester, MN, USA

Introduction: A 19 year old female with symptomatic palpitations was found to have sustained

wide complex tachycardia

Methods: N/A

Results: Echo was completely normal. She underwent EP study. She has normal interval

measurements at the baseline with no pre-excitation (A). During tachycardia the shortest AV

interval was 152 msec. During the tachycardia a premature ventricular contraction (PVC) delivered

at a perfect time showed fusion with resetting consistent with macro re-entry tachycardia (B). Burst

right ventricle apex pacing initiated the tachycardia with fusion present confirmed again the

tachycardia mechanism. The post pacing interval (PPI) tachycardia cycle length (TCL) confirmed

that it is far from the circuit (C). Entrainment from pacing at His showed perfect PPI-TCL which

will not be expected if this was ventricular tachycardia with such morphology. The previous

findings were due to antidromic re-entry tachycardia using left lateral antegrade only, decremental

accessory pathway (AP). This was confirmed with premature atrial contraction during tachycardia

and delivered during refractory septal A and showed advancement of the next V and the next A,

consistent with an antegrade AP participating in the tachycardia. In image (B) the findings were

due to advancing the next A from the PVC which advanced the next V. In image (D) the findings

were due to His capture since His is part of the circuit. Two interesting findings were seen as well:

The AP was adenosine sensitive. RFA was done during tachycardia and with significant wobbling

in TCL (450-730 msec) as typically seen in accelerated junctional rhythm and terminated with A.

Conclusion: Patient did well, with no recurrence.

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PEDIATRIC CARDIOLOGY AND CARDIAC SURGERY / CONGENITAL HEART DISEASE

300

A RARE CASE OF PLATYPNEA-ORTHODEOXIA IN A PATIENT WITH PFO S. Vinnakota1, D.F. Kupsky2, S.H. Wan2, W. Miranda3, C.S. Rihal3

1. KMC Manipal, Manipal University, India

2. Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

3. Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA

Background: Platypnea-Orthodeoxia (POS) is a rare syndrome of hypoxia and dyspnea worsened

by assuming the upright position. The most common etiology is intracardiac right to left shunting

of blood across a Patent Foramen Ovale (PFO) or ASD. With modern interventional techniques,

treatment can be done through minimally invasive trans-catheter closures.

Case: 72-year-old woman with prior ischemic stroke and PFO presented with POS causing

functional decline over 4 months and inability to tolerate any activity during this time. On

examination, she was tachycardic and dyspneic, with oxygen saturation of 75 in the upright and

leaning forward position while on 3L oxygen. Saturation rebounded to 88-89 with recumbency.

Laboratory evaluation was unremarkable. Chest X-Ray was normal. CT Chest ruled out pulmonary

embolism. Given her history of stroke along with platypnea-orthodeoxia causing significant

functional impairment, trans-catheter closure of PFO was performed resulting in complete

resolution of symptoms.

Discussion: This case demonstrates an exceedingly rare syndrome in a patient with a PFO

presenting with classical symptoms of POS- dyspnea and hypoxia that worsened in the upright

position. After ruling out other causes for postural accentuation of right to left shunt, PFO closure

was performed, completely resolving her symptoms. Development of POS requires two

conditions: an anatomical defect leading to inter-atrial communication and a functional component

causing shunt redirection with normal pulmonary or right atrial pressures. This syndrome is most

frequently attributed to major pulmonary disorders, but may also be seen with cirrhotic vascular

abnormalities. Closure of the PFO reverses the orthostatic hypoxia and often permanently resolves

symptoms as in our patient’s case. Less than 200 cases of this uncommon syndrome have been

described to date in literature. As percutaneous closure of PFOs result in a favorable prognosis,

alternate treatment modalities have not been explored adequately due to the relative rarity of this

interesting phenomenon.

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301

CHYLOUS TAMPONADE DUE TO CATHETER INDUCED SUPERIOR VENA CAVAL

OBSTRUCTION IN A PREMATURE INFANT P. Asrani, M. Sahni, A.M. Aly, S.K. Jain


Pediatric chylopericardium is a rare complication of thoracic duct injury during cardiothoracic

surgeries. It could also be a potential complication of superior vena cava (SVC) obstruction. We

report a rare case of chylous tamponade in a premature infant as a complication of prolonged

central venous catheterization. A thirty-six week gestation premature female infant was born with

congenital diaphragmatic hernia. She developed severe pulmonary hypertension that required

ECMO for the first 8 days of life. Surgical repair was performed at 2 weeks of age. The patient

required central venous catheterization in the SVC via the right internal jugular vein for

administration of medications and hyper-alimentation. At 3 months of age, she developed

respiratory distress and edema of the upper chest, head and neck. Chest X-ray showed enlarged

cardiac silhouette. Echocardiogram showed normal cardiac anatomy and a large pericardial

effusion causing diastolic collapse of the right atrium consistent with cardiac tamponade. Urgent

pericardiocentesis was performed with aspiration of 50 cc of milky fluid that had triglycerides 413

mg/dl, protein 4.2 g/dl, WBC 6963/dl with 89% lymphocytes, suggestive of chylous pericardial

effusion. A pigtail catheter was placed for continuous drainage of the fluid. A magnetic resonance

venogram showed no clear flow related enhancement in both internal jugular vein and SVC with

small collaterals visualized in the neck. This indicated complete obstruction of both veins. The

patient continued to accumulate a significant amount of fluid despite being on octreotide. A

surgical pericardial window was created with gradual clinical improvement. There was complete

resolution of the swelling by 4 months of age. This is a rare case of SVC obstruction in a premature

infant causing massive chylous pericardial effusion without surgical injury of the thoracic duct.

This obstruction was likely caused by thrombus formation or vessel wall smooth muscle

proliferation due to catheter-induced injury.

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302

HYPERALDOSTERONISM COMPLICATING CONGESTIVE HEART FAILURE DUE

TO A LEFT TO RIGHT SHUNT IN A PREMATURE INFANT S. Dasgupta, A.M. Aly, S.K. Jain


Congestive heart failure (CHF) develops in infants with significant left to right shunt lesions as

the pulmonary vascular resistance drops after birth. The medical management includes diuretics

and angiotensin converting enzyme inhibitors (ACEI) as afterload reducing agents. We report a

31 week gestation premature male infant who presented with a heart murmur in the NICU shortly

after birth. An echocardiogram showed a large membranous VSD and a moderate size PDA. He

had normal serum electrolytes on day 5 of life. At 2 weeks of age, he developed respiratory distress

that required mechanical ventilation. A CXR showed cardiomegaly and pulmonary edema

consistent with CHF. He was initially treated with furosemide and captopril without any significant

improvement in 3 days. Routine basic labs showed severe hypokalemia (1.9 mmol/L) that did not

respond to IV KCL supplementation. Other positive labs included elevated NT-proBNP to 22,700

pg/ml (nl <125 pg/ml), hypernatremia (149 mmol/L), increased urinary potassium excretion to

111.8 mmol/L (nl <10 mmol/L) and decreased urinary sodium excretion to <5 mmol/L (nl 20-40

mmol/L). These results were suggestive of hyperaldosteronism which was confirmed with serum

aldosterone of 547.5 ng/dl (nl 7-99 ng/dl). The addition of spironolactone (an aldosterone

antagonist) had a dramatic effect within 2 days as CHF symptoms improved clinically and the

patient was extubated. The serum aldosterone level dropped to 109.3 ng/dl other lab values became

normal. In this patient, the decreased renal perfusion due to CHF led to activation of the renin-

angiotensin-aldosterone system and eventually the development of hyperaldosteronism and

hypokalemia which was resistant to IV KCL infusion. The addition of an aldosterone antagonist

to diuretics and ACEI was shown to be helpful in this situation. Also, NT-proBNP seems to be a

useful biochemical marker for CHF that correlates well with the clinical picture.

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HEART VALVE DISEASE – CAUSES, SYMPTOMS, DIAGNOSIS AND TREATMENT

303

WATCHFUL OBSERVATION VERSUS EARLY AORTIC VALVE REPLACEMENT

FOR SYMPTOMATIC LOW-GRADIENT SEVERE AORTIC STENOSIS D-H Kang1, J-Y Jang1, S-J Park2, S-M Lee1, D-H Kim1, K-J Choi1, J-H Zo3, J-W Lee1

1. Asan Medical Center, Seoul, South Korea

2. Samsung Medical Center, South Korea

3. Boramae Hospital, South Korea

Background: The timing of aortic valve replacement (AVR) remains controversial in symptomatic

patients with normal flow, low-gradient severe aortic stenosis (AS) and preserved left ventricular

ejection fraction (LVEF). We sought to compare long-term mortality of early AVR versus a

watchful observation strategy.

Methods: From 2000 to 2011, we prospectively evaluated 284 consecutive symptomatic patients

(136 men, age; 68±10 years) with normal flow, low-gradient severe AS and preserved LVEF who

were potential candidates for early AVR. Low-gradient severe AS was defined as indexed aortic

valve area < 0.6 cm2/m2 with mean gradient < 40 mmHg. Early AVR was performed on 98 patients

(early AVR group) while the watchful observation strategy was selected for 186 patients (watchful

observation group). Patients in the watchful observation group were referred for AVR if mean

gradient ≥ 40 mmHg during follow-up.

Results: There were no significant differences between the early AVR and the watchful

observation group in the risk of overall mortality (HR 0.94 for the early AVR; 95% CI, 0.51 to

1.73; P = 0.84) or in the estimated actuarial 10-year mortality rates (28 ± 8% vs. 29 ± 5%, P =

0.84) in the overall cohort. Lower STS score, lower comorbidity index, female gender and

performance of AVR were independently associated with overall survival on multivariable Cox

analysis. For 80 propensity-score matched pairs, the risk overall death was not significantly

different between the two groups (HR 1.62 for the early AVR; 95% CI, 0.71 to 3.67; P = 0.25).

Conclusions: The early AVR does not improve survival in symptomatic patients with normal flow,

low-gradient severe AS and preserved LVEF. Watchful observation with timely performance of

AVR should be considered a therapeutic option.

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304

USE OF CONDUITS IN PATIENTS WITH PROHIBITIVE ILIO-FEMORAL ARTERY

ANATOMY FOR TRANSCATHETER AORTIC VALVE REPLACEMENT V.A. Doraiswamy, M. Trinidad, K. Subramanian, M. Szerlip, A. Abidov, K. Lotun

University of Arizona, Tucson, AZ, USA

Introduction: The FDA has approved transcatheter aortic valve replacement (TAVR) for the

treatment of severe aortic stenosis. Large bore sheaths are required for delivery of the prosthetic

valve, which limits the patient population to whom TAVR may be offered. We present our initial

experience with iliac conduits to expand the patient selection criteria for TAVR Aortic. Charts and

imaging of 28 consecutive patients who underwent TAVR between 7/8/2012 and 8/7/13 at the

hospital were reviewed. Data on iliac arterial anatomy and postoperative complications were

collected. Among these, 5 patients with complex iliac anatomy had an iliac conduit placed. The

conduits were 10 mm polyester grafts sewn proximally onto the common iliac artery to provide

unobstructed access to the aorta. After the procedure the conduit was partially removed to leave a

patch angioplasty on the artery.

Results: Vascular complications occurred in 0 number of patients. 1 patient had transient

paresthesia over upper thigh which resolved at 4 weeks follow up. Beside the 5 patients with iliac

conduits, 15 underwent a regular TF approach with surgical exposure of the common femoral

artery, and 3 underwent a TA approach.

Conclusion: There are only few case reports of iliac conduits being used to bypass severe

iliofemoral disease. Our case series include only 5 patients. In patients with severe iliofemoral

disease and with localized iliofemoral disease, and centers were TAVR are in the initial phase and

attempts to reduce the complications rates, conduit approach might be a better choice. Other

alternatives like retroperitoneal exposure, followed by direct aorta or iliac artery access avoiding

the use of prosthetic conduit and eliminating the need for more extensive retroperitoneal

dissection, which has been used for endovascular aortic repair, yet need to be studied and applied

for difficult iliac anatomy in TAVR.

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305

LEFT ATRIAL APPENDAGE VELOCITY IMPROVEMENT POST TRANSCATHEER

AORTIC VALVE REPLACEMENT RESULTS IN BETTER OUTCOMES T. Ando1, D. Slovut2, C. Taub2

1. Mount Sinai Beth Israel, New York, NY, USA

2. Montefiore Medical Center, Bronx, NY, USA

Objectives: To assess whether better improvement in left atrial appendage (LAA) emptying

velocity (LAAEV) after transcatheter aortic valve replacement (TAVR) are associated with better

outcomes.

Background: LAAEV is reflective of LAA function.

Methods: LAA velocities were consecutively recorded before and after TAVR with

transesophageal echocardiography between 2012-2015 at a single center. Patients were

categorized into two groups; group 1: LAAEV improvement more than 5cm/sec, group 2: LAAEV

improvement less than 5 cm/sec. Primary endpoint was composite of death, admission for heart

failure, stroke and acute coronary syndrome within 12 months. Patients with persistent atrial

fibrillation and patients with TAVR related complications were excluded.

Results: Forty-three consecutive patients were included in the study. Mean age was 80 ± 8 years

and male was (22/43, 49%). LAAEV before and after TAVR was 34.8 ± 17.4 (cm/sec) and 38.9 ±

22.6 (p=0.05). During median follow up of 31 (3-555) days, 9 patients had reached primary

endpoints. Kaplan-Meier curve showed lower event rates for group 1 (Log-lank p=0.046,

Figure 1).

Conclusions: Better improvement in LAAEV was associated with better outcome after TAVR in

this pilot study. This measurement may serve as simple markers for TAVR prognosis.

Figure 1

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306

BALLOON MITRAL VALVULOPLASTY IN MIRROR IMAGE DEXTROCARDIA

WITH RHEUMATIC MITRAL STENOSIS P.K. Grant, C.N. Makhale, V.V. Nivargi, J.B. Bhalke, S.J. Subhedar, S.N. Deore

Ruby Hall Clinic -Grant Medical Foundation, Pune, India

Objective: To demonstrate the safety of balloon mitral valvuloplasty in patients of rheumatic mitral

stenosis and situs inversus with dextrocardia

Background: Distorted cardiac anatomy and cardiac malpositions increase the complications of

interatrial septal puncture and left ventricular entry during balloon mitral valvuloplasty.

Methods: Five patients with rheumatic mitral stenosis and situs inversus with dextrocardia were

included in this study .Mean transmitral gradient before balloon mitral valvuloplasty (18 +/- 6

mmHg) was significantly higher, while mitral valve area (MVA) (0.68 +/- 0.4 cm2) was

significantly lower All the five patients were young (mean age of 32 years) and symptomatic (mean

pulmonary artery pressure 60 +/- 10 mmHg). Left femoral venous and arterial approach was used.

Fluoroscopic imaging was performed without inverting the images although the software for the

same was available. The interatrial septum was approached using fluoroscopy guide with needle

directed towards the spine and keeping the pointer of Brockenbrough needle at seven to eight o’

clock position followed by transatrial puncture in left lateral view. The transit across the mitral

valve was done in left anterior oblique view without using pseudo right anterior oblique imaging

with just clockwise or counterclockwise guidewire movement. Simultaneous transthoracic

echocardiography guidance was used

Results: Pre and post balloon mitral valvuloplasty hemodynamic parameters were compared. After

balloon mitral valvuloplasty, mean PA pressure was significantly reduced– [33.5 +/- 12 mmhg],

with a significant reduction in transmitral gradient (8.2 +/- 3.5 mmHg), with an increase in mitral

valve area (2.1 +/- 0.6cm2).

Conclusion: This case series demonstrates the safety and efficacy of balloon mitral valvuloplasty

without inverting the images on fluoroscopy.

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307

SEVERE BICUSPID AORTIC VALVE (BAV) REGURGITATION IN A

DYSFUNCTIONAL AND DILATED NON-COMPACTED LEFT VENTRICLE: A CASE

REPORT A.L. Schenone1, A.H. Cohen1, D. Majadalany2

1. Cleveland Clinic Medicine Institute, Cleveland, OH, USA

2. Cleveland Clinic Heart and Vascular Institute, Cleveland, OH, USA

Background: Bicuspid aortic valve (BAV) is the most common congenital heart disease. Up to

20% of asymptomatic adults with BAV present with moderate to severe valve insufficiency.

Limited data exists regarding surgical indications and outcomes in the setting of BAV with severe

LV dilatation, LV systolic dysfunction or LVNC.

Methods: We present a case report about a 32 year old male with a severe case of dilated

cardiomyopathy in the setting of severe BAV regurgitation and LVNC syndrome. This patient

upon presentation had no prior cardiac history and presented with a chief complaint of dyspnea on

exertion and chest pain. Echocardiogram revealed the aortic valve as bicuspid with an eccentric,

posteriorly-directed, severe aortic regurgitation originating between the right and non-coronary

cusps. There were mild mitral and moderate pulmonic regurgitations. The decision to undergo

surgical aortic valve replacement was made after extensive cardiac assessment, including stress

testing, cardiac catheterization and cardiac MRI with good early outcomes.

Discussion: Our case represented the most extreme, documented presentation in the spectrum of

BAV with dilated and dysfunctional, non-compacted LV. The case was complicated by the

presence of left ventricle (apical and lateral wall) non-compaction; a common distribution in

patients with BAV. Overall, LVNC patients with larger LVEDD, NYHA III-IV or chronic atrial

fibrillation carry worse prognoses. Management reports of patients with LVNC requiring cardiac

surgery are limited, and the impact of LVNC on myocardial protection strategies is not known.

Delineation of the myocardial function, presence of ventricular thrombi, and inducible arrhythmias

must be known when considering surgery.

Conclusion: There exists uncertainty in the management of the patient with regurgitant BAV with

severe left ventricular dilatation, due to a lack of specific guidelines. Therefore, further research is

warranted to provide guidelines for the care of such patients.

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308

HEPARIN VERSUS BIVALIRUDIN IN TRANSCATHETER AORTIC VALVE

IMPLANTATION M. Greif1, P. Lange1, S. Sadoni2, D. Jochheim1, J. Mehilli1, S. Massberg1, C. Kupatt1

1. University of Munich Department of Cardiology, Munich, Germany

2. University of Munich Department of Cardiac Surgery, Munich, Germany

Background: We aimed to compare safety and efficacy of direct thrombin inhibitor bivalirudin to

unfractionated heparin during transcatheter aortic valve implantation (TAVI).

Methods: In this retrospective analysis, 459 patients underwent TAVI between 2007 and 2012,

338 patients received bivalirudin, and 121 patients received UFH. In the bivalirudin group, the

Sapien XT valve was implanted in 158 (46.9%) patients, while 179 (53.1%) received a Medtronic

CoreValve. In the heparin group, only Medtronic CoreValve was implanted. The primary outcome

of interest was the incidence of any bleeding. Secondary outcomes of interest were all cause

mortality and cardiovascular mortality at 72 h post-procedure and 30 days.

Results: No significant difference between the groups was observed for life-threatening bleeding

(2.4% for bivalirudin vs. 3.3% for heparin, p=0.59), major bleeding (8.3% vs. 8.2%, respectively,

p=0.98) and minor bleeding (8.3% vs. 7.4%, respectively, p=0.76). At 72 h post-procedure, all-

cause mortality was 3.0% in the bivalirudin group and 3.3% for the heparin group (p=0.88),

whereas cardiovascular mortality was 3.0% in the bivalirudin group and 2.5% in the heparin group

(p=0.77). At 30 days, all-cause mortality was 5.3% vs. 4.1% in the bivalirudin and heparin groups

(p=0.57) and cardiovascular mortality was 4.4% vs. 2.5% (p=0.33). Device success (VARC-2

composite endpoint) was 94.0% in bivalirudin-treated and 92.6% in heparin-treated patients

(p=0.60). The Early Safety at 30 days was 85.3% in the bivalirudin treated group compared to

83.6% in the heparin group (p=0.65).

Conclusions: Bivalirudin has a similar safety and efficacy profile as weight adjusted UFH during

TAVI procedure.

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309

IMPACT OF LVH BY ECG VOLTAGE CRITERIA ON TRANS-CATHETER AORTIC

VALVE REPLACEMENT OUTCOMES A.G. Marthy1, A. Delago2,3, A. Elkharbotly1,2, B. Bulibek1,2, M. El-Hajjar1,2,

M. Torosoff1,2


2. Albany Medical Center, Albany, NY, USA

3. Capital Cardiology Associates, Albany, NY, USA

Background and hypothesis: The association of Left Ventricular Hypertrophy (LVH) by

electrographic voltage criteria and trans-catheter aortic valve replacement (TAVR) outcomes has

not been investigated. LVH is expected in patients with severe aortic valve stenosis undergoing

TAVR. Absence of LVH by voltage criteria may be indicative of “burned-out” cardiomyopathy

and portend a poor prognosis.

Methods: A retrospective chart review was conducted in 200 consecutive TAVR patients. ECG

data was collected and stratified into LVH (yLVH n=51), and normal wall thickness (noLVH

n=149). Outcomes were adjudicated according to the PARTNER trial definitions (NEJM 2010;

363: 1597-1607). Analyses of variation, correlation, chi-square, and logistic regression were used.

The study was approved by the institutional IRB. Results: There was no association between any

LVH and previous CVA, PVD, previous smoking history, hyperlipidemia, hypertension, or

diagnosis of COPD. In addition, LVH was not associated with significant difference in age at time

of procedure (83.0 +/- 1 vs. nLVH 81.8 +/- 0.6 years old; p=0.35), renal function (Cr 1.3 +/- 0.1

vs. noLVH: Cr 1.5 +/- 0.1 mg/dL; p=0.278), aortic valve area (0.746 +/- 0.025 vs. noLVH: 0.776

+/- 0.48 squared cm; p=0.672), aortic valve gradient (43.3 +/-2.2 vs. noLVH: 44.1 +/- 1.5 mmHg;

p=0.788), LV ejection fraction (49.7 +/- 1.7 vs. noLVH 49.8 +/- 0.9%; p=0.95), and length of stay

in ICU (146 +/- 33 vs nLVH: 117 +/- 7 hours; p = 0.203). Similarly, LVH was not associated with

an increased incidence of post-TAVR death, re-hospitalizations, stroke, or acute renal failure.

Conclusion: Presence or absence of LVH by ECG voltage criteria in TAVR patients is not

associated with significant differences in valve area, ejection fraction, or co-morbidities. And more

importantly, it does not lead to inferior TAVR outcomes.

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310

ECHOCARDIOGRAPHIC EVALUATION OF LEFT VENTRICULAR DIASTOLIC

FUNCTION AFTER CLOSED MITRAL VALVOTOMY D. Kaushal, S.K. Singh, R. Kumar, V. Devenraj

King George's Medical University, Lucknow, Uttar Pradesh, India

Background: Mitral stenosis is frequent valvular complication of rheumatic heart disease, leading

to reduced LV filling during diastole, causing diastolic dysfunction. The aim of this study is 2D

Echocardiographic Evaluation of left ventricular diastolic function after closed mitral valvotomy

in rheumatic mitral stenosis.

Methods: This is a single centre one-year comparative study consisting of twenty nine patients of

rheumatic severe mitral stenosis. We analyzed preoperative and post operative transthoracic 2D

echocardiographic parameters of diastolic function and compared both data to evaluate

improvement of diastolic function in all patients who underwent closed mitral valvotomy.

Results: 29 patients underwent successful operation; average age was 34.97 ± 9.74 with 62.1%

females. Maximum patients were in NYHA grade 3 (69.0%) and 4 patients were in AF. Wilkins

score ranged from 6 to 10. MVA increased from 0.77 ± 0.13 to 2.32 ± 0.26, EF increased from

61.38 ± 4.61 to 64.79 ± 3.22, DT (ms) decreased from 231.55 ± 49.31 to 168.28 ± 14.30, E/A ratio

reverted to 1.70 ± 0.54 from 0.89 ± 0.39. TEI index improved from 0.50 ± 0.03 to 0.39 ± 0.06,

MIPV (cm/sec) increased from 47.28 ± 3.71 to 57.86 ± 3.19. In peri-operative and follow up, there

was no incidence of Mitral regurgitation and thrombo-embolic incident. There was no mortality.

Conclusion: Surgical closed mitral valvotomy produce excellent and comparable early

hemodynamic improvement, significant improvement in clinical stage of disease and improvement

in diastolic function.

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311

ROLE OF UNUSUAL PREDICTORS OF PERIVALVULAR AORTIC

REGURGITATION POST TRANS-CATHETER AORTIC VALVE REPLACEMENT

S. Banga, A. Aggarwal, K. Narala, M. Barzallo, S. Mungee

OSF St. Francis Medical Center, University of Illinois College of Medicine at Peoria, IL, USA

Background: Clinical outcome in Trans-catheter aortic valve replacement (TAVR) is affected by

presence of post-procedure peri-valvular aortic regurgitation (PAR). We studied the role of pre-

procedural and intra-procedural factors in predicting PAR post TAVR.

Methods: Data for all patients who underwent TAVR from December 2012 to September 2014

were retrospectively studied. Predictors including age, gender, BMI, preexisting aortic

regurgitation, pre-procedural left ventricular ejection fraction (LVEF) and size of the prosthetic

valve (Edwards Sapien, Edwards Lifesciences, Irvine, California). were studied for their relation

to the presence of PAR after TAVR. Patients were divided into Group A, having post-TAVR PAR

and Group B without post-TAVR PAR. Statistical analysis was done using Fischer test.

Results: Of the total 54 patients who underwent TAVR, 37 patients were included in Group A and

17 patients in Group B with 56.8% versus 47% were males (p= 0.566)and 78.4% versus 76.5%

had pre-existing AR(p= 1.0) respectively. See Table 1.

Conclusions: Pre-existing aortic regurgitation, LVEF and size of the implanted prosthetic valve at

aortic position are not predictors of PAR post-TAVR procedure. The role of demographic factors

like age, gender and BMI is also not significant in the pathogenesis of post –TAVR PAR. Further

large studies will be needed to search other possible predictors.

Table 1.

Predictors Group A (n=37)

Mean± SD

Group B (n=17)

Mean± SD

p-value

Age 83.2 ± 6.4 84.9 ± 4.3 .253

BMI 29.7±5.9 28.3±5.9 .411

LVEF 56.49±13.9 60.6±9.3 .209

Size of prosthetic valve 24.8±1.8 24.6±1.5 .684

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312

OUTCOMES OF PATIENTS UNDERGOING CONCOMITANT AORTIC AND

MITRAL VALVE SURGERY IN THE PHILIPPINE HEART CENTER FROM YEAR

2000 - 2013

A.C.L. Jayme

Philippine Heart Center, QC, Philippines

Background: There has been a steady increase in cardiac valve surgery performed for concomitant

aortic and mitral disease in the Philippine Heart Center. Although the frequency of double valve

surgery (DVS) remains low compared to isolated valve surgery, more patients are undergoing the

said procedure.

The main objective of this paper is to examine the outcome of patients undergoing DVS at the

Philippine Heart Center in terms of in-hospital mortality and postoperative complications.

Methodology and Results: This is a report of a retrospective study of the 312 patients who

underwent AV and MV surgery from 2000 to 2013 at the Philippine Heart Center. In-hospital

mortality was 7.9% and was higher for men, patients with smaller BSA and those who had

concomitant CABG. The most common post-operative complication was pulmonary for the

majority of patients. The more common complication noted among those who died was renal

failure requiring dialysis.

Conclusion: The in-hospital mortality for the Philippine Heart Center for DVS from 2000-2013 is

7.9%. The center’s in-hospital rate was lower compared to those published by Hannan et al,

Galloway et al, and Hellgren et al. Reports in these centers noted mortality ranging from 14-18%.

The most common postoperative complication for all patients was pulmonary and the most

common complication for those who died was acute renal failure requiring hemodialysis.

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ADVANCES IN CARDIAC SURGERY: SURGICAL REVASCULARIZATION, MECHANICAL CIRCULATORY SUPPORT / CARDIAC TRANSPLANTATION / CARDIAC MYXOMA

313

AN UNUSUAL CAUSE OF HEMOPTYSIS DURING PREGNANCY A. Singh, S. Kort

Suny-Stonybrook University Hospital, Stonybrook, New York, USA

A 25year old female, 27 weeks pregnant, presented to our institution for evaluation of two episodes

of hemoptysis. She described the amount to be 4-5 tablespoons each time. In addition, she also

reported feeling short of breath on exertion for a week prior to presentation. She denied any

symptoms of cough, fever, chills, weight loss, pleuritic chest pain, asymmetric leg swelling, sick

contacts, recent travel outside the country or similar symptoms in her previous pregnancy. Vitals

were noted to be stable. Physical exam was significant for a diastolic murmur at the apex and trace

pitting edema in bilateral lower extremities. Laboratory tests revealed normal hematocrit, platelets,

coagulation factors and liver function tests. Chest x-ray was significant for mild pulmonary

congestion. Transthoracic echocardiogram revealed a severely dilated left atrium and a large

(4.5cmX2.4cm), pedunculated, mobile, left atrial mass, attached to the inter-atrial septum, causing

obstruction to the left ventricular inflow. This was considered to be most consistent with an atrial

myxoma. The mean transmitral gradient was calculated to be 18mmHg corresponding to severe

mitral stenosis. An interdisciplinary meeting was called to decide on the optimal timing of tumor

resection. After careful review of available options and patient consent, a decision was made to

proceed with surgery with careful monitoring of fetus intra-operatively. The patient underwent

open heart surgery and resection of the tumor successfully with no adverse events to the fetus. She

was subsequently discharged with close follow up and delivered a healthy full term fetus at 39

weeks by repeat cesarean section. There is paucity of data to guide management of patients with

left atrial myxoma causing functional mitral stenosis during pregnancy and this case is an example

of a favorable outcome from early intervention in such cases.

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314

POST ORTHOTOPIC HEART TRANSPLANTATION COMPLICATED BY

DISSEMINATED BLASTOMYCES T. Yousuf1, H. Keshmiri1, J. Kramer2



Introduction: Post transplant immunosuppression is necessary to prevent organ rejection. This

immunosuppression, however, can lead to a host of complications arising from opportunistic

infections. We present a case of disseminated blastomycosis manifested only as a skin lesion in an

asymptomatic patient post-orthotopic heart transplantation.

Case: A 64-year old female who had recently undergone orthotopic heart transplant for end-stage

ischemic cardiomyopathy presented for a scheduled routine cardiac biopsy. A crusted plaque was

observed at the nasal tip. This started six months after surgery as a pimple that she repeatedly tried

to extract by squeezing, which resulted in redness and crust formation. Her immunosuppressive

and prophylactic medications included: Mycophenolate, Tacrolimus, Prednisone, Bactrim,

Acyclovir, Valganciclovir, Pyrimethamine/Sulfadiazine, and Fluconazole. On physical exam she

was flushed, with a large and exquisitely tender crusted necrotic lesion involving almost the entire

half of the nose anteriorly, the left forehead and right side of the neck. She had decreased air entry

over the right lung field. Chest CT showed bilateral nodular pulmonary infiltrates with confluence

in the posterior right upper lobe. Blood cultures for aerobes/ anaerobes were negative. Both

Excisional biopsy of the nasal cutaneous ulcer and bronchial biopsy, demonstrated numerous

fungal yeast forms morphologically consistent with Blastomyces. Cultures of both specimens grew

Blastomyces dermatitidis, with MRSA superinfection of the nose. She received 14 days of IV

Amphotericin B for disseminated blastomycosis and 7 days of IV Vancomycin for MRSA. Her

symptoms and cutaneous lesions improved and she was maintained on Itraconazole treatment for

one year.

Discussion: This case illustrates a delicate balance that must be struck between suppressing the

immune response to prevent graft rejection and avoiding over-immunosuppression that can lead

to susceptibility to infection. Thus, in any post transplant patient, clinicians should watch out for

any signs of infection even if the patient is asymptomatic.

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315

LEFT ATRIAL MYXOMA PRESENTING AS PAROXYSMAL ATRIAL

FIBRILLATION M.A. Zulqarnain, A. Ali, M. Ali, M.K. Syed, M.T. Mujtaba

Wake Forest Baptist Health, Winston Salem, North Carolina, USA

Introduction: We present a case of large left atrial myxoma causing functional mitral stenosis with

initial presentation of new onset atrial fibrillation.

Case Presentation: 55 year old female with past medical history significant for hypertension and

diabetes presented with generalized weakness, fatigue, lightheadedness, shortness of breath and

palpitations for the past two weeks. In the ER, she was found to be in atrial fibrillation and

subsequently converted to normal sinus rhythm. Physical examination revealed a diastolic flow

sound in the apical region. Echocardiogram revealed a moderately dilated left atrium with a large

(2.5 x 4.7) myxoma attached to the interatrial septum which was prolapsing into the left ventricular

cavity with irregular borders creating a functional mitral stenosis with valve area estimated at 1.1.

Surgical opinion was sought and patient underwent minimally invasive atrial myxoma resection

through anterior minithoracotomy. The patient tolerated the procedure well and her symptoms

resolved. She has been doing well since then.

Discussion: Myxomas are the most common primary cardiac tumors and about 75% are in the left

atrium. Initial suspicion for myxomas is reported to be as low as 5.7%. Systemic embolization is

present in about 30% of patients and valvular obstruction can sometimes result in sudden cardiac

death. Left ventricular failure caused by partial obstruction of the mitral valve orifice by the

myxoma can also be observed. Myxomas might be initially misdiagnosed as mitral stenosis, but

severe mitral stenosis, as seen in our patient has been described in only 14% of cases. A diastolic

murmur on auscultation is found in 64-67% of cases while classical tumor plop sound is found in

15% of cases. Myxomas are benign and have excellent long term prognosis with low recurrence

rate after surgical resection. Myxomas should be considered in the differential diagnosis in patients

with suspected mitral valve disease.

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316

PREGNANCY RELATED SPONTANEOUS CORONARY ARTERY DISSECTION:

WHEN PCI WAS NOT ENOUGH M.A. Zulqarnain, M.T. Mujtaba, M. Ali, M.K. Syed

Wake Forest Baptist Health, Winston Salem, North Carolina, USA

Introduction: We present a young otherwise healthy female with no cardiac risk factors with chest

pain, initially normal EKG and elevated cardiac biomarkers with spontaneous LAD dissection.

Case Presentation: A 28 year old female who had an uncomplicated vaginal delivery 5 days ago,

presented to the ER with sudden onset of chest pain. This was associated with shortness of breath

and diaphoresis. Her cardiopulmonary exam was benign. Initial set of cardiac enzymes revealed

CK-MB of 76 and Troponin 0.08. Cardiac enzymes were progressively elevated. A stat bedside

echocardiogram revealed anteroseptal and apical akinesis. Emergent cardiac catheterization

revealed an acute spirally dissected LAD through the proximal mid-segment, with 90% stenosis.

The lesion was successfully stented using three drug eluding stents. Within an hour of the

procedure, her chest pain recurred, and the EKG showed ST elevations, with non sustained

ventricular tachycardia. A second catheterization revealed retrograde propagation of the dissection

into the proximal LAD and back into the left main trunk. She underwent emergent CABG, from

which she recovered well.

Discussion: Spontaneous coronary dissection should be considered in any young female patient

without a previous cardiac history or risk factors, who presents with cardiac arrest or an acute

coronary syndrome. The optimal management is unclear because of the limited clinical experience.

Emergent coronary angiography followed by PCI or CABG is likely to offer the best survival. In

pregnant women, dissection may be a consequence of increased hemodynamic stress or of

hormonal effects on the arterial wall. Postpartum status is present in 18% women with mean

postpartum period of 38 days.ST-elevation myocardial infarction (STEMI) is present in 49% of

cases. The left anterior descending coronary artery is the most frequently affected vessel. Specific

guidelines still need to be established.

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CARDIOVASCULAR DISEASE PREVENTION AND RISK FACTORS

317

BODY MASS INDEX AND MORTALITY IN A VERY LARGE COHORT: IS IT

REALLY HEALTHIER TO BE OVERWEIGHT? A.L. Klatsky1, J. Zhang2

1. Northern CA Kaiser Permanente Division of Research, Oakland, CA, USA

2. Miramonte High School, Orinda, CA, USA

Purpose: To study risk of death in relation to body mass index (BMI) in 273,843 free-living

persons.

Background: Despite substantial published literature controversy persists about the optimal level

of body weight. The overall BMI-mortality risk is J-shaped, with underweight persons and obese

persons at increased risk. Many experts define “normal”

BMI as 18.5-24.9 kg/m2, with 25-29.9 kg/m2 as “overweight” and ≥30 kg/m2 as “obese”.

Obesity is subdivided into 30-34.9 kg/m2 (grade I), 35-39.9 kg/m2 (grade II) and ≥40kg/m2

(grade III). Studies consistently show higher mortality for grade II-III obesity, but results conflict

for the “overweight” category and even grade I obesity.

Methods: We used logistic regression with 8 covariates including smoking; the BMI referent was

18.5-24.9 kg/m2.

Results: With average follow-up of >30 years, there were 103,218 deaths, 41,215 attributed to

cardiovascular (CV) causes and 62,003 to non-CV causes. Hazard ratios (HR) and [95%

confidence intervals] for all deaths in relation to BMI were: <18.5=1.1 [1.0-2.0], 25-29=1.1 [1.1-

1.2], 30-34=1.5 [1.4-1.5], 35-39=2.1 [1.9-2.3], and ≥40=2.7 [2.4-3.0]. Increased risk of persons

with BMI below 18.5 kg/m2 was concentrated in non-CV deaths; for CV deaths these persons had

a HR of 0.7 (0.6-0.7). For the overweight and grade 1 obesity categories, the HRs were 1.4 and 1.8

for CV deaths; for non-CV deaths these HRs were 1.0.

Conclusions: These data show the importance of examining causes of death when considering

risks associated with underweight, overweight and obesity. For risk of CV death it is better to be

thin.

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318

MEDITERRANEAN DIET: FROM HISTORY TO CULTURE TO MEDICINE

D. Panagiotakos

School of Health Science, Harokopio University, Athens, Greece

Cardiometabolic diseases and cancer dominate the health status of the majority of westernized

populations. In the context of dietary control, Mediterranean diet has been proposed as a healthy

eating dietary pattern based on evidence that greater adherence to this diet is associated with lower

all-cause and disease-specific survival. Its origins begin thousands years ago, in Mediterranean

basin, in the middle 1960s this dietary pattern came to surface. Although there is not one

Mediterranean diet, a high consumption of foods of vegetable origin, such as fruits, vegetables,

legumes, nuts, cereals and whole-grains; olive oil as the principal source of fat; fish and poultry

consumed in low-to-moderate amounts; relatively low consumption of red meat; and moderate

consumption of wine, normally with meals, could be considered the most dominant characteristics

of this dietary pattern.

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319

STATE-OF-THE-ART CVD PREVENTION: LOOKING BEYOND AND

INTERPRETING THE ACC/AHA PREVENTION OF CARDIOVASCULAR DISEASE

GUIDELINES

N.D. Wong

University of California, Irvine, CA, USA

The ACC/AHA released evidence-based guidelines on cardiovascular disease (CVD) risk

assessment, lifestyle, obesity, and cholesterol management. The risk assessment guideline

recommended a new “Pooled Cohort Equations” calculator to estimate 10-year and lifetime risk

of atherosclerotic CVD (ASCVD), and other measures-- premature family history of CVD, C-

reactive protein, ankle brachial index, and coronary calcium scores to further stratify risk and

inform the treatment decision. The lifestyle guideline focused on dietary patterns and physical

activity for blood pressure and LDL-cholesterol reduction and the obesity guideline highlighted

the importance of multiple intensive personalized sessions with lifestyle interventionalists and the

value of moderate weight loss in control of risk factors. The cholesterol guideline focused on the

identification of four statin eligible groups: ASCVD, diabetes, LDL-cholesterol >=190 mg/dl, and

>=7.5% 10-year risk of ASCVD, but emphasizing the importance of the clinician-patient risk

discussion when considering initiation or intensification of therapy. While the guideline does not

support specific initiation or target LDL-C levels, emphasis is on therapeutic response, still

requiring regular monitoring of LDL-C, and non-statin agents can be considered if needed

response is not achieved. The IMPROVE-IT results as well as emerging data on newer agents

provide promising opportunities to address lipid residual risk in persons not adequately tolerating

or responding to statins. Other criteria to address residual risk such as consideration of non-HDL-

C levels have been recommended by the recent National Lipid Association guideline. Finally,

recent blood pressure guidelines have recommended revised cutpoints for blood pressure control

where benefit has been shown. Coordinated efforts for composite risk factor control, electronic

medical record adoption of risk assessment tools, identification of providers’ patients not adhering

to recommended therapies, and e-health-based personalized CVD management strategies will be

important steps to implement these guidelines and achieve further progress in CVD prevention

efforts.

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320

GENDER DIFFERENCES AND HEALTHY AGING

E.L. Barrett-Connor

UC San Diego School of Medicine, La Jolla, CA, USA

Forty years ago, few cohort studies of cardiovascular disease (CVD) included women and fewer

still included diabetes or glycemia as risk factors. I describe here the Rancho Bernardo Study

(RBS), a single-site, >40-year cohort study of sex differences in heart disease and how diabetes

modifies women's natural cardioprotection. More than 6,000 participants were followed for

morbidity and mortality, with nearly 3,000 survivors (and death certificates for >85% of

decedents). In RBS, more than one-half of diabetes cases were undiagnosed without an oral

glucose tolerance test (OGTT); more women than men had isolated post-challenge hyperglycemia

as their only glucose evidence of diabetes; men had more diabetes, with higher fasting but lower

post-challenge glucose levels than did women; women with diabetes had more classic CVD risk

factors than did men; and excess risk factor clustering partially explained how diabetes eradicates

female cardioprotection. Post-challenge glucose was a stronger CVD risk factor than was fasting

glucose. Endogenous insulin was not an independent CVD risk factor in women or men. Men with

higher testosterone levels developed fewer cases of diabetes and had fewer metabolic syndrome

components. In men, higher total testosterone levels predicted reduced risks for all-cause and CVD

but not cancer mortality. In women, both extremes of bioavailable testosterone predicted fatal

coronary heart disease but not all-cause mortality. Summary point estimates from large systematic

reviews of individual data have replicated most RBS findings. Ongoing research can further clarify

how diabetes modifies women's cardioprotection from mid-life to old age. Future research may

also identify if and how lifestyle variables influence gender differences and healthy aging.

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321

CARDIOVASCULAR RESPONSES TO THREATFUL CHALLENGES IN PERSONS

WITH HIGH TRAIT ANXIETY D. Jezova1, N. Hlavacova1, R. Duncko1, P. Solarikova2, M. Marko2, I. Brezina2

1. Institute of Experimental Endocrinology, Laboratory of Pharmacological Neuroendocrinology,

Slovak Academy of Sciences, Bratislava, Slovakia

2. Department of Psychology, Faculty of Philosophy, Comenius University, Bratislava, Slovakia

An optimal cardiovascular response to threatening challenges is indispensable for coping with the

situation. Anxiety disorders and high anxiety as a personality trait have been expected to be

associated with autonomic lability and hyperreactivity during stress. Data published on this topic

are rather variable. We have performed a series of studies in healthy humans and patients to clarify

the relationship between anxiety and cardiovascular activation under stress conditions. In a group

of healthy volunteers with high trait anxiety, we have observed an exaggerated hear rate (HR)

response during psychosocial stress compared to non-anxious individuals. However, in contrast to

general expectations, plasma epinephrine and norepinephrine responses were lower in anxious

subjects. Treatment of anxious subjects with a mixture of aminoacids lysine and arginine (10 days)

was able to normalize stress-induced catecholamine responses. We have revealed that the influence

of trait anxiety on cardiovascular activation is gender dependent. Anxious women in the follicular

phase of the menstrual cycle exhibited a greater stress-induced rise in systolic blood pressure

compared to anxious women in the luteal phase and to non-anxious women in both phases.

Accordingly, we have brought evidence for a reduced neuroendocrine response to stressors in

patients with an anxiety disorder or with immune dysfunction accompanied by anxiety. Patients

with different types of allergy showed increased trait anxiety and attenuated heart rate response

during psychosocial stress. Similarly, the activity of alpha-amylase, an enzyme activated by the

sympathetic nervous system, was reduced in patients compared to controls. In conclusion, high

trait anxiety appears to be associated with impaired coordination of the stress response, rather than

global hypo- or hyper-responsiveness.

Supported by APVV-0496-12.

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322

ASSOCIATION OF MODIFIABLE LIFESTYLE FACTORS AND RISK OF TOTAL

AND CARDIOVASCULAR MORTALITY AMONG OLDER US MALE PHYSICIANS

L. Djoussé


Background: While previous studies have reported beneficial effects of healthy lifestyle factors on the risk

of major chronic diseases and mortality in younger adults, only limited data are available for older adults.

Objective: We sought to test the hypothesis that being ideal on few simple and modifiable factors (smoking,

exercise, diet, body weight, and alcohol consumption) is associated with a lower incidence of total,

cardiovascular disease, and cancer mortality among male physicians aged ≥65 years at baseline.

Methods: Prospective study of 8,321 male physicians from the Physicians’ Health Study (PHS) who

completed a food frequency questionnaire between 1999 and 2001. Information on lifestyle factors was

self-reported at baseline and death was ascertained by the PHS endpoint committee. Ideal factors were

current non-smokers, body mass index below 25 kg/m2, vigorous exercise, alcohol intake of 1-2 drinks/d,

and being in the top two quintiles of the alternate Healthy Eating Index. We used Cox proportional hazard

model to estimate adjusted hazard ratios with 95% confidence intervals according to the number of

prevalent ideal factors at baseline.

Results: Mean age was 73.2 years (range: 65.0 to 97.6 y) and 95% of study participants were Caucasian.

During a mean follow up of 9 years, 1600 subjects died (including 444 CVD deaths and 505 cancer deaths).

There was an inverse association between the number of ideal lifestyle factors met and the incidence of

death (Fig.1). Compared to subjects meeting ≤ 1 factor, hazard ratios (95% CI) for CVD death were 0.79

(0.59-1.04), 0.80 (0.60-1.04), and 0.57 (0.41-0.79) for meeting 2, 3, and 4+ ideal factors, after adjustment

for age and prevalence of CVD, hypertension, cancer, heart failure, atrial fibrillation, and diabetes at

baseline, p trend 0.002. Corresponding values were 0.70 (0.55-0.90), 0.58 (0.45-0.74), and 0.51 (0.38-0.67),

p trend <0.0001 for cancer deaths and 0.65 (0.52-0.82), 0.67 (0.54-0.84), and 0.55 (0.43-0.71), p trend

<0.0001 for other causes of death. While no interaction was seen between number of ideal factors and

prevalent diabetes, hypertension, cancer, or CVD on the risk of death, this relation was stronger in subjects

<75 y [adjusted HR: 1.0 (ref), 0.60 (0.49-0.74), 0.55 (0.44-0.68), and 0.44 (0.34-0.57) for ≤ 1, 2, 3, and 4+

ideal factors, p trend <0.0001] than in subjects 75+ y [corresponding HRs: 1.0 (ref), 0.82 (0.67-1.00), 0.80

(0.66-0.97), and 0.65 (0.52-0.80), p trend 0.0001], p for interaction 0.02.

Conclusion: Even at older age, adherence to healthful lifestyle factors is associated with a lower incidence

of total and cause-specific mortality in male physicians. These data suggest that even among older adults,

it may still be important to recommend healthful behaviors to reduce mortality.

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323

ASSESSMENT OF CARDIOVASCULAR PROGNOSIS IN DIABETIC PATIENTS. THE

ROLE OF CARDIAC IMAGING

A. Elhendy

Marshfield Clinic, Marshfield, WI, USA

Diabetes mellitus is major risk factor for cardiovascular disease and associated complications.

Cardiovascular disease may be silent or presents with atypical symptoms due to autonomic

neuropathy and therefore, many patients with minimal or no symptoms remain at high risk of

morbidity and mortality. Cardiovascular imaging plays a major role in the diagnosis and risk

stratification of coronary artery disease in diabetic patients. In patients who are able to exercise, a

normal stress echocardiogram identifies patients at low risk. The pattern of multi-vessel

abnormality is associated with a dramatic increase in cardiac events with approximately a third of

these patients developing cardiac death and non -fatal myocardial infarction within a few years

after the test. Myocardial contrast imaging during dobutamine stress test is a promising tool and

offers improved sensitivity at submaximal heart rate and allows incremental risk assessment.

Myocardial perfusion imaging with radionuclide techniques is widely used and has a well

established diagnostic and prognostic value. However, even after a normal study, diabetic patients

remain at higher of cardiac events compared to non diabetic patients with a normal imaging study.

The low risk warrantee period after a normal imaging study is shorter in diabetic versus non

diabetic patients which necessitate closer follow of high risk patients. Coronary calcium scoring

is useful in detecting early phase of atherosclerosis and provides objective information to predict

cardiac events. CT angiography may serve as a gate keeper for invasive angiography with a high

sensitivity. Prognostic value is established, but information is largely influenced by early

revascularization. Limitations include artifacts, irradiation and risk of contrast nephropathy. A

careful understanding of the advantages and limitations of anatomical and functional imaging

techniques allows better guide for risk assessment, implementation of aggressive preventive

therapy and selection of patients who may benefit from revascularization.

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324

TIME OF ONSET OF CARDIAC EVENTS: DOES GENDER MATTER? R. Manfredini1, A. De Giorgi1, F. Fabbian1, F. Signani2, M. Gallerani3, R. Salmi3

1. School of Medicine, University of Ferrara, Italy

2. Azienda Unità Sanitaria Locale, Ferrara, Italy

3. Azienda Ospedaliero-Universitaria, Ferrara, Italy

Background: Various acute cardiovascular diseases exhibit predictable-in-time 24-hour, weekly

or seasonal patterning in their nonfatal and fatal events, e.g., myocardial infarction, sudden cardiac

death, abdominal, aortic, and thoracic dissections, venous thromboembolism, hemorrhagic and

ischemic stroke.

Objective: Knowledge of these temporal patterns not only helps guide patient care, but research of

their underlying endogenous mechanisms and external triggers aimed to the development and

application of effective preventive and therapeutic strategies. However, no particular attention has

been devoted to the existence of possible gender-related differences in the time of onset of life-

threatening events.

Methods: We performed a systematic review of the literature of the last two decades dealing with

temporal patterns of cardiovascular events.

Results: Two hundred and fourteen items were found. Eighty-four studies (total: ~1.640,000

people) focused on circadian aspects, 41 (total: ~2,040,000 people) focused on weekly aspects,

and 89 (total: ~2,400,000 people) focused on seasonal aspects. Although the majority of studies

(170 out of 214, 79%) provided information on number of cases in men/women subgroups, only

less than one third (29%) performed separate analyses by gender and reported results for circadian

(26/84, 31%), weekly (13/41, 32%), and seasonal (23/89, 26%) onset of events. For each disease,

single patterns by gender will be presented.

Conclusions: Many different pathogenetic mechanisms may explain the existence of a temporal

variation in the onset of acute cardiovascular diseases, and possible differences by gender.

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325

NEW INSIGHTS INTO SEX-BASED DIFFERENCES IN HEART DISEASE

S. Malik

University of California, Irvine, USA

The role of coronary microvascular dysfunction (CMD) has now been more widely accepted as

having a role in those with symptomatic non-obstructive coronary artery disease. However, the

role of CMD in women compared to men is only recently being explored. Risk factors that

predispose to CMD will be discussed. We will also discuss the sequela of CMD, including heart

failure with preserved ejection fraction, Takasubo’s cardiomyopathy, and sudden death. We will

also discuss the role of stress in modulating endothelial dysfunction. Finally, both

pharmacological and non-pharmacological treatment of CMD will be discussed.

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326

CARDIAC DYSFUNCTION SUBSEQUENT TO EXPOSRE TO OZONE; AN AIR

POLLUTANT

R. Sethi

California Health Sciences University, Clovis, California, USA,

Even though a number of advancements have been made toward identifying the risks associated

with cardiovascular disease (CVD), and these have resulted in a decline in mortality, many patients

with cardiac disease show no established previous risk. It appears other unknown factors contribute

to the pathophysiology of CVD. Out of 350,000 sudden cardiac deaths each year in the United

States, 60,000 deaths have been linked to air pollution, suggesting a detrimental role of

environmental pollutants in the development of CVD. The present study tested the hypothesis that

chronic ozone (O3) exposure enhances the sensitivity to myocardial dysfunction. Sprague Dawley

rats were continuously exposed for 8 hrs/day for 28 and 56 days to filtered air or 0.8 ppm O3. In-

vivo cardiac function measured as LVDP, +dP/dt, –dP/dt and LVEDP after 24 hours of exposure,

was significantly decreased and increased respectively in ozone exposed animals compared to rats

exposed to filtered air. Attenuation of cardiac function subsequent to ozone exposure was

associated with increased myocardial TNF alpha levels and lipid peroxidation as well as decreased

myocardial activities of superoxidase dismutase (SOD) and IL-10. These data suggests an ozone-

induced enhanced sensitivity to myocardial injury may be due to promoting levels of oxidative

stress and increased activity of inflammatory mediators.

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FROM MECHANISMS TO FUTURE DIRECTIONS IN THE TREATMENT AND MANAGEMENT OF HEART FAILURE

327

ADJUDICATED VERSUS ADMINISTRATIVE HEART FAILURE WITH PRESERVED

EJECTION FRACTION A.P. Kalogeropoulos1, A. Patel1, S. Li1, L. Papadimitriou2, G. Burkman1,

V.V. Georgiopoulou1, J. Butler2

1. Emory University, Atlanta, GA, USA

2. Stony Brook University, Stony Brook, NY, USA

Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with readmission and

mortality rates similar to HF with reduced ejection fraction (HFrEF). No disease-modifying

therapy for HFpEF exists to date, partially because of the multifactorial pathophysiology of HFpEF

and the heterogeneity of patients. Studies from administrative databases report that HFpEF

represents 40%-60% of HF cases. However, limited prospective data suggest a lower proportion,

and enrollment in recent HFpEF trials has been slower than anticipated, suggesting that (1) the

proportion of HF patients fulfilling all clinical criteria for HFpEF may be considerably lower and

(2) administrative data may not have been as specific to exclude patients with recovered ejection

fraction (HFrecEF) or specific cardiomyopathies. Therefore, more detailed data are needed on

HFpEF epidemiology in order to properly design clinical trials. In a study of 1752 outpatients who

received care associated with designated ICD-9 codes between 01/01/2012 and 03/31/2012 in

Emory Healthcare (Atlanta, GA), we confirmed the diagnosis of HF in 1652 patients (94.3%).

After individual adjudication, we classified 19.4% as HFpEF, 16.2% as HFrecEF; and 60.0% as

HFrEF, while 4.3% had HF due to special causes. In comparison, the proportion of HFpEF cases

based of ICD-9 codes and last EF without adjudication would have been 39.0%. HFpEF patients

were older, more likely to be female, and had a higher burden of comorbidities compared to

HFrecEF. After 2 years, age- and gender- adjusted mortality was 10.2% in HFrEF, 8.6% in HFpEF,

and 4.4% in HFrecEF patients (stratified log-rank P=0.005). We concluded that (1) the proportion

of clinically verified HFpEF is considerably lower compared to administrative estimates; (2) many

patients with preserved EF actually represent HFrecEF, which has a more favorable prognosis;

and (3) a large number of HFpEF patients would not be eligible for clinical trials due to serious

concomitant conditions.

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328

THE HEART FAILURE CLINIC: TAKING CENTER STAGE IN CHRONIC DISEASE

MANAGEMENT

M.A. Silver

University of Illinois, Chicago, IL USA

Acute decompensated heart failure, because of its dramatic, albeit often insidious presentation,

high intensity acute care requirement and relatively high in-patient mortality has dominated our

focus on what “is” heart failure. The reality is that the major focus needs to shift towards viewing

heart failure as a chronic disease, with often predictable (and preventable) exacerbations, that

requires active, lifelong management and innovation. The heart failure clinic has been variably

designed and implemented but often has been structured with parallel capabilities of in-patient

care, focusing on acutely optimizing fluid and electrolyte status, normalizing filling pressures and

augmentation of guideline driven medical strategies.

The heart failure clinic therefore finds itself with a broader mission for patients, families and

providers. A reasonable structural framework for the topography of heart failure care include

understanding the entire series of transitions for the patient, their physiology and the goals of care

in various post-acute care periods including early and late transitions phases, a relative plateau

phase and for most at some point an advanced heart failure and/or palliation phase.

Trained heart failure workers and standardized goals and approaches lead to improved outcomes,

heart failure literacy and satisfaction with this chronic disease state.

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329

BEYOND THE GUIDELINES - NEW OPTIONS FOR TREATING HEART FAILURE

IN 2015

M.R. Johnson

University of Wisconsin, Madison, Wisconsin, USA

The updated ACCF/AHA Guideline for the Management of Heart Failure is not even 2 years old,

however, trials have suggested new potential treatment options for heart failure with reduced

ejection fraction (HFrEF). Two of these trials will be reviewed. Resting tachycardia is a poor

prognostic factor in HFrEF pts. Indeed, beta-blockers may improve HFrEF outcomes in part by

decreasing heart rate. The SHIFT trial evaluated ivabradine (inhibitor of If current in the sinoatrial

node) in HFrEF pts with LVEF <35%, in sinus rhythm with heart rate >70, and a HF hospitalization

in the previous year on guideline directed medical therapy (GDMT), including a beta-blocker if

tolerated. At 22.9 months follow-up, 24% of ivabradine vs 29% of placebo pts reached the primary

endpoint of cardiovascular death or HF hospitalization (HR 0.82, p<0.0001). Ivabradine caused

fewer serious adverse events, but more bradycardia and visual side effects. SHIFT suggests that

ivabradine is beneficial when the heart rate remains >70 in HFrEF pts on GDMT. The

PARADIGM-HF Trial evaluated the combined angiotensin receptor-neprilysin inhibitor LCZ696

(valsartan-sacubitril) vs enalapril in class II-IV HFrEF pts with LVEF <40%. The trial was

stopped after 27 months when the boundary for benefit with LCZ696 was crossed. The primary

outcome (cardiovascular death or first HF hospitalization) occurred in 21.8% of LCZ696 vs 26.5%

of enalapril pts (HR .80, P<0.001). LCZ696 also decreased mortality, cardiovascular death, and

HF hospitalization. LCZ696 produced more hypotension, but less renal impairment, hyperkalemia

and cough. Although the study was met with enthusiastic acclaim for the benefits of LCZ696,

concerns have been raised about the trial’s enalapril dose (10 mg bid) and the fact that 70% of pts

had class II HF. The exact role of ivabradine and LCZ696 in future HFrEF therapy remains to be

determined.

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330

LEFT VENTRICULAR VS. BIVENTRICULAR MECHANICAL SUPPORT FOR

FAILING HEARTS: MAIN CHALLENGES BEFORE DECISION MAKING

M. Dandel

Deutsches Herzzentrum, Berlin, Germany

Left ventricular assist devices (LVADs) are safer and provide better survival and better quality of life than

biventricular assist devices (BVADs) but end-stage heart failure often involves both ventricles, even

if its initial cause was left-sided heart disease. Right ventricular failure (RVF) is also a severe

complication in about 25% of patients receiving a LVAD, with high perioperative morbidity (renal,

hepatic or multi-organ failure) and mortality. Patients who receive an RV assist device (RVAD)

only days after LVAD insertion fare much worse than those who receive an RVAD simultaneously

with LVAD implantation. Temporary RVAD support in LVAD recipients with high risk for

postoperative RVF can avoid permanent BVAD support. Thus, patients who definitely need a BVAD

should already be identified preoperatively or at least intra-operatively. However, although the initial

biochemical, hemodynamic and echocardiographic patient profile at admission may suggest the need

for a BVAD, many risk factors may be favorably modified by various strategies that may result in avoidance

of RVF after LVAD implantation.

The lecture summarizes the knowledge of risk factors for irreversible RVF after LVAD implantation

and strategies to optimize RV function (preoperatively, intra-operatively and post-operatively) aimed to

reduce the number of BVAD implantations. Special attention is focused on assessment of RV size,

geometry and function in relation to loading conditions with the goal of predicting preoperatively the RV

changes which might be induced by RV afterload reduction with the LVAD. The lecture aimed also to

provide a theoretical and practical basis for clinicians intending to be engaged in this field.

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331

BIVENTRICULAR SUPPORT - TOTAL ARTIFICIAL HEART

F. Arabia

Cedars-Sinai Medical Center, Los Angeles CA, USA

The management of advanced HF has evolved over the last decades. With better understanding of

HF pathophysiology, new pharmacological agents have been introduced that have resulted in

improvements in survival. For those patients that fail to improve, mechanical circulatory support

with LVADs and total artificial hearts (TAHs) have served as a beneficial bridge to transplantation

(BTT). The TAH has continued to play a significant role as a BTT in patients with biventricular

failure and more selected indications that could not be completely helped with LVADs. Improved

survival with the TAH has resulted in more patients benefiting from this technology.

Improvements will eventually lead to a totally implantable device that will permanently replace

the failing human heart.

The majority of the experience is with the SynCardia TAH. The original series in 1992, showed

survival of 62% (30 days). In 2004 the survival to transplantation was 79% versus 46% (control).

A series in 2009 reported on 100 patients who received the TAH. Of these patients, 91% had an

INTERMACS profile 1. Survival to transplantation was 68.3%, while the most common cause of

death was multiple organ failure. Strokes occurred in 7.9% of the patients. The TAH continues to

be used as BTT in patients with severe biventricular failure (i.e., INTERMACS profile 1 and

profile 2) .However, the last few years has seen an increase in its use and a better understanding

of the indications for its implementation. Newer indications for BTT include: hypertrophic and

restrictive cardiomyopathies, chronic graft failure post heart transplantation, arrhythmias

unresponsive to conventional therapies, congenital abnormalities, RV failure post LVAD

implantation or failure, cardiogenic shock secondary to postinfarction VSD, amyloidosis, cardiac

malignancies and Chagas’ disease.

Newer TAH’s include the Carmat TAH and BiVACOR TAH. The TAH continues to have an

increasing role in the management of advance heart failure.

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332

INTERVENTIONS USING THE ELECTRONIC MEDICAL RECORD TO IMPROVE

CARE OF PATIENTS WITH HEART DISEASE

P.A. Heidenreich

VA Palo Alto HCS, Stanford University, Palo Alto, CA, USA

The increased use of electronic medical records has created an opportunity to impact clinical

decisions through reminders or other clinical decision support. This presentation will discuss

several randomized trials of interventions that use the medical record to impact provider

prescribing practices for patients with heart disease. Several trials of heart failure care will be

discussed with outcomes of increased use of angiotensin converting enzyme inhibitors, beta-

blockers and implantable cardioverter defibrillators in appropriate patients. Recent, unpublished

data will be presented from a trial testing an intervention to reduce inappropriate

echocardiography. Specifically, I will discuss how a note to the physician at the end of the

echocardiography report that recommended for or against a follow-up study had an impact on

subsequent testing. Potential barriers to implementing these interventions will be discussed. Data

on the cost and impact will demonstrate that these types of interventions have a small but

significant impact on treatment and their very low cost makes them a good value (highly cost-

effective).

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333

REDUCTION OF 30-DAY ALL-CAUSE READMISSION IN HEART FAILURE:

CURRENT EVIDENCE AND FUTURE DIRECTIONS

A. Ahmed

The Washington DC VA Medical Center. Washington, DC, USA

Heart failure is a leading cause of hospital readmission in older adults. About a quarter of all

hospitalized heart failure patients are readmitted within 30 days of discharge. The Affordable Care

Act, the new United States healthcare reform law, has created provisions for financial penalties for

hospitals with higher than expected 30-day all-cause readmission rates older Medicare

beneficiaries. Eager to avoid this penalty hospitals are adopting strategies for transitions of care

based on variable and inconsistent associations with 30-day all-cause hospital readmission from

single center reports, post hoc analyses, and observational studies. Data from our peer-reviewed

publication demonstrated that digoxin reduces 30-day all-cause hospital admission in ambulatory

older patients with chronic systolic heart failure and that in Medicare beneficiaries with systolic

heart failure, a discharge prescription of digoxin was associated with lower 30-day all-cause

hospital readmission, which was maintained at 12 months, and was not at the expense of higher

mortality. We have also demonstrated that ACE inhibitors, but not beta blockers, may similarly

reduce 30-day all-cause readmission in heart failure patients with reduced ejection fraction.

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334

COENZYME Q10 AS AN ADJUVANT THERAPY IN HEART FAILURE (HF) A. Kumar, V. Mohan, K. Harharpreet

Govt. Medical College/G.N.D. Hospital, Amritsar, India

Congestive heart failure has become a global epidemic and its prevalence is increasing with the

increasing longevity of life and improvements in management of acute coronary syndrome,

hypertension and diabetes mellitus. It is the number one cardiac cause of hospitalizations in

patients above 60 years and has a prognosis worse than most of malignancies. None of the

conventional and newer treatments of HF have made any significant improvement in mortality and

morbidity. Coenzyme Q10 (CoQ10) levels have been found to be consistently low in HF in most

of reported studies. CoQ10 by improving oxidative phosphorylation at mitochondrial levels

improves cellular bioenergetics of cardiac muscle cells and also by its antioxidant, vasodilatory

and membrane stabilizing effects produces symptomatic improvement when added to the

conventional treatment. In our own study, the addition of CoQ10 (100-200mg/day) to conventional

decongestant therapy led to significant improvement in Quality Of Life and 6 Minutes Walk Test

with reduced number of hospitalizations and reduction in development of refractory stage thereby

decreasing the requirement for assisted cardiac devices and cardiac transplantations. Recent

international Q SYMBIO trial has also shown improvement in symptoms and MACE with some

mortality reduction with CoQ10 use in HF. Thus CoQ10 can be recommended as an important

adjuvant therapy in HF.

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335

ULTRAFILTRATION THERAPY FOR ACUTE HEART FAILURE; WHERE ARE WE

STANDING IN 2015?

A.K. Kazory

University of Florida, Gainesville, Florida, USA

The negative prognostic impact of congestion and worsening renal function in patients with

decompensated heart failure has been widely recognized. As diuretics are thought to contribute to

deterioration of kidney function in this setting, attempts have been made to develop therapeutic

strategies that are not fully based on diuretic use in this setting. Extracorporeal ultrafiltration

represents an intriguing therapy for patients with heart failure that presumably lacks the adverse

impact of diuretics on renal function while portending a number of biological advantages such as

higher efficiency for sodium removal and restoration of diuretic responsiveness as observed in

several clinical trials. However, conflicting data have recently emerged in relation to some of the

previously proposed effects possibly due to counterbalance of the potential negative mechanisms

and other less understood factors. In this talk, the existing evidence on the efficiency and safety of

conventional therapy for acute decompensated heart failure is briefly reviewed. Then the potential

role of ultrafiltration in this setting and the advantages of this therapeutic modality over

conventional management strategies are discussed along with the results of the most recent trials.

At the end, controversial aspects of ultrafiltration therapy for heart failure (e.g. indications for use

and impact on mortality) are explained in detail.

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336

COGNITIVE IMPAIRMENT IN CHRONIC HEART FAILURE

K. Alagiakrishnan


Heart Failure and Cognitive Impairment (CI) are medical conditions that are frequently seen in

older adults. Heart failure has been shown to be associated with CI beyond that seen in normal

aging, and indeed the risk of CI is four times higher in patients with heart failure when compared

to age-matched controls. The spectrum of cognitive impairment includes delirium, isolated

memory or non-memory related deficits and dementia. Both heart failure with reduced and

preserved ejection fraction has been shown to be associated with defects in different domains of

cognition. Various pathophysiological mechanisms related to heart failure can contribute to

cognitive decline. In different studies, CI in heart failure has been associated with higher rates of

functional impairment, mortality and interference with self-care. Poor adherence to medication

regimens and self-care management of heart failure is possible in patient with cognitive problems

and it could be a cause for readmissions. Validated tools and criteria should be used to differentiate

acute cognitive decline or delirium from chronic cognitive decline or Mild Cognitive Impairment

(MCI)/Dementia. These conditions are not routinely screened for in clinical practice settings with

heart failure population and guidelines on optimal assessment strategies are lacking. Certain heart

failure treatment approaches and strategies may help to reduce cognitive decline in these subjects.

Early detection of CI may help to improve clinical outcomes in older adults with heart failure.

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VALVULAR HEART DISEASE MECHANISMS AND TREATMENT OPTIONS

337

INCREASING UTILIZATION OF THE BIOPROSTHETIC VALVE IN PATIENT

UNDER 60- REAL WORLD EXPERIENCE CONTRARY TO GUIDELINE

RECOMMENDATION M. Kawabori, J. Ejiofor, S. McGurk, M. Yammine, L. Cohn, S. Aranki, T. Kaneko


Objectives: To analyze increasing utilization of bioprosthetic aortic valves in patients under age

60.

Background: The 2014 American College of Cardiology/American Heart Association

(ACC/AHA) guidelines recommend mechanical valves for patients under age 60. Although

bioprosthetic valves are preferred for ease of management, the risk of reoperation from

deterioration is a major concern for young patients. We assessed this trend in our patients and

compared outcomes by device type.

Methods: We analyzed 6,421 patients undergoing primary aortic valve replacement (AVR) from

1994 to 2014. Of these, 1297 were under age 60.

Results: The mean age was 49.7 (+/- 8.2) years, and 31% were women. Concomitant coronary

bypass was performed in 21.7% and mitral valve procedures in 16.1%. Operative mortality was

2.2%. Before 2002, mechanical valves were implanted in 78% of patients while after 2003;

mechanical valves were implanted in only 45% (Figure 1, P<0.001). Mechanical valves were

implanted in younger patients (48.3±8.6 vs 51.4±7.5, p=0.001) and those on preoperative warfarin

(2.9% vs 0.7%, p=0.004). The mechanical valve group trended toward higher operative mortality

(2.9% vs 1.2%, p=0.054), but no long-term survival advantage.

Conclusions: Contrary to ACC/AHA recommended guidelines, our study showed increase use of

bioprosthetic valves during AVR in patients under age 60 with similar long-term outcomes.

Figure 1: showing trend of valve type for patients <60 who underwent isolated AVR

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338

CIRCULAR SHAPE ASSUMPTION OF OVAL LVOT BY STANDARD 2D

ECHOCARDIOGRAPHY (CONTINUITY METHOD) MAY RESULT IN

SUBSTANTIAL UNDERESTIMATION OF AORTIC VALVE AREA

M. Roberts, A. Samim, C. Katikireddy

Division of Cardiology, UCSF Fresno, Fresno, CA, USA

Objective: Our aim of the study is to estimate the degree of underestimation of the aortic valve

area by standard 2D echocardiography continuity method.

Background: Currently by 2D echocardiography (echo) continuity method, we make circular

assumption of oval shaped left ventricular outflow tract (LVOT) that may result in underestimating

aortic valve area (AVA) and overestimating the degree of aortic stenosis (AS).

Methods: We retrospectively identified 46 AS patients with normal flow who underwent gated

computed tomorgraphy (CT) and echo. We estimated AVA by echo (continuity method 1). We

re-calculated the AVA by continuity method 2 in which echo derived Doppler flow is used in

conjunction with CT derived LVOT diameter (average of minimum and maximum). We estimated

the differences in AVA quantification between the two methods and their ability to distinguish

severe from non-severe AS based on transvalvular gradients (figure) and dimensionless velocity

index (DVI).

Results: AVA by continuity method 1 was significantly smaller compared to continuity method 2

(p<0.01). AVA estimation by continuity method 2 had a better diagnostic sensitivity (77%) with

similar specificity (84%) compared to continuity method 1 (62% sensitivity; 84% specificity), in

discriminating non-severe from severe AS, as determined by transvalvular gradients and DVI.

Conclusions: Standard echo may significantly underestimate the aortic valve area. Our study

findings explain the discrepancy in AS severity we encounter when the stenosis is severe by valve

area, however the transvalvular gradients are only moderately elevated (despite normal flow).

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339

PREDICTION OF NEW ONSET ATRIAL FIBRILLATION AFTER TRANSCATHETER

AORTIC VALVE REPLACEMENT T. Ando1, D. Slovut2, C. Taub2

1. Mount Sinai Beth Israel, New York, NY, USA

2. Montefiore Medical Center, New York, NY, USA

Objectives: To assess the role of left atrial appendage emptying and filling velocity (LAAEV and

LAAFV, respectively) after transcatheter aortic valve replacement (TAVR) in predicting new

onset atrial fibrillation (NOAF).

Background: NOAF after TAVR is a known risk factor for future adverse outcomes. Therefore it

is important to identify patients at risk.

Methods: Medical records of 53 patients who had consecutive LAAEV and LAAFV measured

before and after TAVR with transesophageal echocardiography were retrospectively reviewed.

Those with history of permanent and paraoxymal atrial fibrillation were excluded.

Results: Thirty-five patients were included. Mean age was 79±9 (Male 15/35). Eight patients

developed NOAF. NOAF was associated with longer hospital stay (median of 4 vs 13 day,

p=0.001). Pre and post TAVR LAAEV and LAAFV was 35.2 ± 16.7 and 40.6 ± 23.1 (cm/sec),

(p=0.041) and 30.8 ± 12.5 and 34.1 ± 13.9 (cm/sec), respectively (p= 0.167). Receiver operating

characteristics curve analysis results are shown in table 1. Changes in LAAFV demonstrated better

prediction of NOAF compared to left atrial volume index (AUC 0.789 vs 0.491, p=0.01)

Conclusions: Increase in LAAEV and LAAFV had good sensitivity and specificity, respectively.

These may serve as simple marker to predict NOAF. Further study is warranted to verify these

findings.

Table 1

Table 1

Result of receiver operating characteristics curve analysis

Cut off value AUC 95% CI sensitivity specificity

ΔLAAEV (cm/s) 4.9 0.70 0.53-0.88 88 63

ΔLAAFV (cm/s) 11.5 0.79 0.61-0.97 63 85

AVA index

(cm2/m2)

0.38 0.63 0.41-0.86 75 59

LAVI (ml/m2) 43.8 0.49 0.21-0.69 63 41

TAVR: transcatheter aortic valve replacement, ΔLAAEV: changes in left atrial appendage

emptying velocity, ΔLAAFV: changes in left atrial appendage filling velocity, AUC: area

under the curve, CI: confidential interval, AVA; aortic valve area, LAVI; left atrial volume

index

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340

OUTCOMES OF MITRAL VALVE SURGERY FOR MITRAL STENOSIS A.F. Al Mosa, H. Najm, A. Omair

King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia and

National Guard Hospital, Riyadh, Saudi Arabia

Objectives and Background: Mitral valve replacement procedures with either a bioprosthetic or a

mechanical valve are used to treat mitral stenosis. This study aimed to evaluate the outcomes of

these two procedures.

Methods: A retrospective cohort involving a total of 195 mitral stenosis patients who have

undergone mitral valve replacement with either bioprosthetic (n=50) or mechanical (n=145) valves

in our institute from 1999 to 2012. Data were analyzed for mortality, functional class,

echocardiographic findings, valve-related complications, and survival. Chi Square test, logistic

regression, Kaplan Meier curve, and dependent proportions tests were some of the tests employed

in the analysis.

Results: Out of 195 patients, 104 (53%) patients could be reached by telephone calls for collecting

long-term outcome information. Twelve patients had late mortality, six in the bioprosthesis group

and six in the mechanical. One patient had perioperative mortality. The Late mortality had

significant association with post-op stroke (P<0.001) and post-op NYHA classes III and IV

(P=0.002). Post-op NYHA class was significantly associated with age (P=0.003), pulmonary

disease (P=0.017), mitral valve type (P=0.011, mechanical valves better), hypertension (P=0.01),

and post-op stroke (P=0.017). NYHA classes were significantly better after the replacement

surgeries (P<0.001). Bioprosthetic valves were significantly associated with worse survival

(P=0.03), worse NYHA post-op (P=0.011), and more re-operations (P=0.006); and borderline

association with late mortality.

Conclusion: Mechanical mitral valve replacement in mitral stenosis patients is associated with less

late mortality, better functional classes, less re-operations, and better survival as compared to

bioprosthetic valves. Stroke occurrence is associated with late mortality and worse functional

classes.

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341

INFECTIOUS ENDOCARDITIS PREVALENCE HAS BEEN INCREASING OVER THE

YEARS WITH PERSISTENTLY HIGHER PREVALENCE IN MALE GENDER M.R. Movahed, M. Hashemzadeh, M. Hashemzadeh

CareMore, University of Arizona, Long Beach VA Health Care System, Tucson, AZ, USA

Background: With better preventive care, we hypostatize that incidence of infectious endocarditis

should decline over the years. The goal of this study was to evaluate the incidence of infectious

endocarditis over the years using a large data base.

Method: The Nationwide Inpatient Sample (NIS) database was utilized to calculate the age-

adjusted prevalence rate of infectious endocarditis in hospitalized patient from 19988 until 2007

based on ICD-9 coding.

Results: We found gradual increase in the prevalence of age adjusted infectious endocarditis over

the last 20 years. Total incidence of infectious endocarditis is also on rise. Furthermore, the age-

adjusted incidence of infectious endocarditis is almost twice in male in comparison to female

gender. Age adjusted in-hospital prevalence of infectious endocarditis was 6.6 per 100,000 in 1988

vs. 7.4 per 100,000 in 2007. Age adjusted in-hospital prevalence of infectious endocarditis was 4.2

per 100,000 in 1988 in female vs. 10.6 per 100,000 in male. For 2007, age adjusted prevalence of

infectious endocarditis was 11.4 per 100,000 in male vs. 5.3 per 100,000 in female. (p<0.01).

Conclusion: Age adjusted prevalence of infectious endocarditis is on the rise over the last 20

years. Furthermore, men have infectious endocarditis rate twice the rate of females. The cause of

this rise and gender difference in the prevalence of infectious endocarditis is not known warranting

further investigation.

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342

ELEVATED SERUM OSTEOPROTEGERIN LEVELS ARE ASSOCIATED WITH

AORTIC VALVULAR STENOSIS: A META-ANALYSIS P. Agasthi1, A. Chenna1, S. Aloor2, P. Kudaravalli3, A. Onwuanyi1


2. Miller School of Medicine, University of Miami

3. University of Nevada School of Medicine, Reno, USA

Background: Aortic valve stenosis (AVS) is a progressive disease involving a cascade of

inflammation and osteogenic abnormalities. Osteoprotegerin (OP) is a member of the tumor

necrosis factor family with pleiotropic effects on bone metabolism, the immune system and

endocrine function. Recent studies have linked elevated serum OP levels with diabetes and

peripheral vascular disease. The association between serum OP and AVS remains obscure.


between circulating OP levels and AVS.


serum OP levels in the patients with AVS and control population. We included case controls,

cohort and cross-sectional studies. We calculated the weighted standardized mean difference

(SMD) in serum OP levels between the AVS and control groups.


participants. The median age of the AVS group was 69yrs. (IQR 69-70) compared to 66yrs. (IQR

63 -69) in the control group. The median female percentage in the AVS group was 45 % (IQR 44-

51%) compared to 45 %(IQR 44-50%) in the control group. The unweighted median serum OP

levels in the AVS group were 6.1 pmol/l (IQR 5.4 – 9) compared to 4.9 pmol/l (IQR 3.6 – 6.4) in

the control group. The SMD of serum OP level was 2.037 (95% CI 0.636 – 3.437) p<0.001

comparing those in the AVS group and control group.

Conclusion: Elevated serum OP levels are significantly associated with presence of AVS. Current

findings warrant the need to further clarify to the role of OP in the development of AVS.

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CURRENT CONCEPTS AND FUTURE DIRECTIONS IN ISCHEMIC HEART DISEASE AND ACUTE CORONARY SYNDROMES

343

WHAT IS OPTIMAL THERAPY FOR STABLE ANGINA IN THE YEAR 2015?

U. Thadani

University of Oklahoma HSC and VA Medical Center, Oklahoma City, OK,USA

In the year 2015, optimal therapy for stable angina comprises of abolition or near abolition of

symptoms, improved quality of life and reduction of the incidence of serious adverse

cardiovascular outcomes (acute myocardial infarction, sudden ischemic cardiac death, unstable

angina and heart failure). Lifestyle modifications (abstinence of smoking, regular exercise) and

lipid modifying treatment with a potent and high dose statin, but not with niacin, or fibrates or with

HLD raising drugs, reduce the incidence of serious adverse cardiovascular outcomes. Daily use

of low dose aspirin, and adequate control of blood pressure also reduce the incidence of serious

adverse outcomes. Older and new antianginal medications, as well as coronary artery

revascularization (percutaneous or surgical) reduce the frequency of angina episodes, increase

angina free exercise duration and improve quality of life, but have little impact on the incidence

of serious adverse cardiovascular outcomes with a few exceptions (use of beta blockers and ACE

inhibitors when left ventricular ejection fraction is reduced and coronary bypass surgery for left

main CAD). Individualization of treatment strategy which takes into account patients’ life style

and presence of comorbidities is essential to achieve this goal. Treatment of refractory angina

despite optimal therapy remains a challenge and newer non-invasive and invasive treatment

strategies are currently under active investigation.

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344

EVOLUTION IN THE MANAGEMENT OF LOW RISK PATIENTS PRESENTING TO

THE EMERGENCY DEPARTMENT WITH CHEST PAIN

E.A. Amsterdam

University of California (Davis) Medical Center, Sacramento, CA, USA

The majority of patients presenting to the ED with chest pain comprise a low risk population who

do not have acute coronary syndrome (ACS) or other life threatening condition. Therefore, most

at are low risk for morbidity and mortality. Such low risk patients are usually identified by

absence of a history of cardiovascular disease, normal or nonischemic ECG, normal initial

troponin, and clinical stability. The utility of accelerated diagnostic protocols (ADP) has been

established for further confirmation of low clinical risk and appropriateness for direct discharge

from the ED versus detection of higher risk patients who require admission. At minimum, these

protocols entail serial ECGs and measurement of cardiac injury markers, both of which can be

performed in the ED or a chest pain observation unit. Negative results have usually been followed

by a cardiac functional (treadmill test or stress imaging evaluation) or anatomic study (cardiac

computed tomography angiography Card [cardiac CTA or MRI) to enhance the safety of early

discharge. These ADPs have been associated with a negative predictive value at 30 days greater

than 99% for ACS or other major cardiovascular event. Several recent protocols for evaluation of

low risk patients have been reported, such as a 2hr evaluation comprising a TIMI risk score of 0,

normal ECGs, and normal hs-TnI. Cardiac CTA has a very high negative predictive value and has

been performed without prior measurement of troponin. Currently, the ADP is in evolution with

recent reports indicating excessive testing of low risk patients and more reliance on physician

discretion for functional or anatomic testing with maintenance of safety and negative predictive

value. This approach has also resulted in shorter length of stay in the ED or observation unit (<6

hr) and lower cost.

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345

CT ASSESSMENT OF CORONARY FLOW PHYSIOLOGY D.S. Berman1, D. Dey1, P. Slomka1, G. Germano1, S.W. Hayes1, J.D. Friedman1,

L. Thomson1, A. Rozanski2

1. Cedars-Sinai Medical Center, Los Angeles, California, USA

2. Mount Sinai-St. Lukes-Roosevelt, New York, NY, USA

Coronary CT angiography (CCTA) is widely accepted as the most sensitive method for detecting

coronary stenosis seen on invasive coronary angiography (ICA). However, the specificity of the

abnormal CCTA for ischemia is low. Three methods for assessing ischemia with CCTA have been

evaluated. CT perfusion (CTP) is performed by adding a CT acquisition during vasodilator stress.

Two multicenter trials have shown good correlation between CT perfusion and evidence of

ischemia by the combination of invasive coronary angiography and SPECT myocardial perfusion

imaging (MPI) or SPECT-MPI alone. A second method evaluates the transluminal attenuation

gradient (TAG) along the length of a coronary artery. A drop in attenuation correlates with the

presence of an ischemic abnormality. This approach has been less completely validated than the

other approaches. Fractional flow reserve by CT (FFR-CT) has recently been developed for

estimating invasive FFR, the current gold standard for lesion-specific ischemia. FFR-CT applies

computational fluid dynamics to a standardly acquired CCTA study. It requires no additional

image acquisition, no additional radiation, and no administration of pharmacologic stress. Three

large multicenter trials have evaluated the accuracy of FFR-CT in predicting invasive FFR. The

most recent trial (NXT) evaluated 484 patients and demonstrated high accuracy (81%) in

prediction of abnormal invasive FFR (≤8 0). The accuracy FFR-CT was higher than that of stenosis

by CCTA or by ICA. The feasibility of using FFR-CT for planning PCI has been recently

demonstrated. Overall, the early data with the various methods of assessing coronary flow

physiology with CCTA suggests that the combination of anatomic and physiologic assessment

with the methods for assessing ischemia as well as coronary plaque--will provide incremental

information in evaluating patients with known or suspected coronary artery disease and may

become part of routine clinical approach to its application.

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346

MYOCARDIAL VIABILITY IN CORONARY ARTERY CHRONIC TOTAL

OCCLUSION

J. Shirani

St. Luke's University Health Network, Bethlehem, PA, USA

Coronary artery chronic total occlusion (CTO) has rapidly become a popular target of percutaneous

coronary intervention (PCI). Technical and technological advances required for approaching these

anatomically complex and challenging lesions have progressed at an extraordinary pace and have

led to amazing success rates. Undoubtedly, many patients with disabling symptoms and failed

medical therapy have been served well with these novel procedures in recent years. Patient

selection, however, has primarily focused on patient symptoms, lesion characteristics, as well as

the state of collateral circulation. Multiple national and international registries have been

established to follow the progress of percutaneous CTO recanalization and have provided valuable

information. Concern, however, exists that this challenging procedure will become the “standard

of care” before its effectiveness and appropriateness is tested in prospective controlled trials. This

presentation will review the current state of patient selection and the need for careful assessment

of the presence and extent of myocardial viability prior to these lengthy, resource intensive and

potentially high risk procedures.

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347

CHOOSING WISELY: WHAT WORKS AND WHAT DOESN’T

G.W. Barsness

Mayo Clinic, Rochester, MN, USA

Background: Contemporary medical care includes numerous practices that are duplicative,

unnecessary and/or potentially harmful. It has been estimated that up to 30% of care activities

may not directly improve patient health or well-being. In this context, the American Board of

Internal Medicine (ABIM) Foundation has developed the Choosing Wisely campaign, an initiative

to help providers and patients engage in conversations about effective care choices. In

collaboration with ABIM, participating provider organizations, including the Critical Care

Societies Collaborative, each created separate lists of “Things to Question,” providing specific,

evidence-based recommendations for providers and patients to use as a framework to discuss care

decisions.

Methods and Results: The Critical Care Societies Collaborative, involving the American

Association of Critical Care Nurses, the American College of Chest Physicians, the American

Thoracic Society and the Society of Critical Care Medicine, has identified “Five Things Physicians

and Patients Should Question.” This list centers on methods to reduce excessive ICU testing,

limiting unnecessary blood transfusions and parenteral nutrition, avoiding inappropriately

aggressive sedation in intubated patients, and enhancing end-of-life care and supportive decision-

making. In addition to this list of questionable practices, there are several potentially underutilized

strategies that can contribute positively to patient outcome, including team-based initiatives such

as infection surveillance and control, as well as integrated efforts to improve patient adherence.

Conclusion: Physician and patient awareness of Choosing Wisely recommendations may result in

enhanced ICU healthcare quality through preservation of increasingly limited healthcare resources

while promoting improved patient outcome.

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348

ENDOTHELIAL DYSFUNCTION FOLLOWING IMPLANTATION OF CORONARY

DRUG-ELUTING STENTS AND MEDICAL THERAPIES

M. Terashima

Toyohashi Heart Center, Toyohashi, Japan

Drug-eluting stents (DES) are widely used for the treatment of coronary artery disease to reduce

the rate of restenosis. However, several studies reported endothelial dysfunction following DES

implantation. Togni et al. reported endothelial dysfunction following sirolimus-eluting stent (SES)

implantation using a bicycle ergometer. Intracoronary administration of acetylcholine (ACh) has

been most frequently used for evaluation of coronary endothelial function. Hofma et al. compared

endothelial dysfunction at 6 months following implantation of SES and bare metal stent (BMS).

They reported that, although no significant change in the vascular diameter was observed in the

BMS group in response to ACh load, lumen diameter reduction was observed after administration

of ACh in the SES group. Kim et al. also demonstrated endothelial dysfunction in patients treated

with SES or paclitaxel-eluting stent (PES) implantation. Moreover, they compared endothelial

function following implantation of BMS, SES, and so-called second generation DES, zotarolimus-

eluting stent (ZES). As a result, both SES and ZES groups had significant endothelial dysfunction

compared to BMS group. Furthermore, its degree was significantly milder in the ZES group

compared to that in the SES group. In addition, endothelial dysfunction may contribute to the

development of severe adverse cardiac events including late/very late stent thrombosis, severe

coronary artery spasms, and neo-atherosclerosis after DES implantation. Therefore, amelioration

of endothelial dysfunction after DES implantation might improve prognosis. At present, several

studies suggested that ACE inhibitors and peroxisome proliferator-activated receptor-gamma

(PPAR gamma) agonists, pioglitazone, may improve endothelial function in the patients with

coronary artery disease. Telmisartan, which has PPAR gamma-mediated effects in addition to its

renin-angiotensin system inhibition effects, has favorable effects on endothelial function. We

previously reported that telmisartan significantly ameliorated endothelial dysfunction after DES

implantation. For the future issues, it is necessary to investigate the impact of these drugs on the

long-term clinical prognoses after DES implantation.

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349

RESPIRATORY MANEUVERS THAT CAN BE USEFUL DURING CARDIAC

CAUTERIZATION OR CORONARY INTERVENTIONS

M.R. Movahed

CareMore, Tucson, Arizona, USA, University of Arizona, Tucson, Arizona, USA

Respiratory maneuvers have been used during invasive cardiac catheterization for improvement in

diagnosis and recently treatment of cardiac disease. These maneuvers are integral part of invasive

assessment and treatment of cardiac patients. It can be divided to maneuvers that can be performed

during right or left heart catheterization. The focus of this lecture are maneuvers that can be useful

mostly during left heart catheterization and interventions. One of the most important maneuver is

performing deep inspiration during catheter advancement into the ascending aorta using right

radial artery access during left heart catheterization. This can facilitated catheter advancement in

to the ascending aorta. The same maneuver can be used when coronary ostia engagement is

difficult during right radial access. The most two important interventional maneuvers that are

recently described by Movahed et al will be discussed in this lecture. One is deep inspiration

maneuver during stent delivery in tortuous native coronary lesions. By instructing a patient to take

deep breath right before stent advancement in difficult cases, stent deliverability can be facilitated

by reducing tortuosity of coronary tree. Opposite maneuver described as reverse Movahed’s

maneuver can be used in tortuous vein graft interventions. As opposed to native coronaries, vein

graft tortuosity is reduced by performing expiration maneuver that can lead to facilitated stent

delivery in difficult vein graft cases by reducing tortuosity in the vein grafts using this maneuver.

These two maneuvers will be extensively discussed in this lecture.

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350

EVOLVING ROLE OF PLATELET FUNCTION TESTING IN ACUTE CORONARY

SYNDROMES R.K. Sharma, J.D. Marsh

University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

The reduction in ischemic events provided by the dual anti-platelet regimen with aspirin and

clopidogrel is extensively published in patients with acute coronary syndrome and patient’s

undergoing percutaneous coronary intervention (PCI). However, there have been several “boxed

warning” on clopidogrel and its variable response which lead to intense controversy on

pharmaokokinetic and pharmacodynamic and pharmacogenomic issues of antiplatelet drugs

especially clopidogrel. Research use of platelet function testing has been successfully validated in

identifying the new anti-platelet drugs like prasugrel and ticagrelor. These platelet function tests

are not regarded as just a laboratory phenomenon anymore; rather a tool shown to predict mortality

in several clinical trials. It is believed that sub optimal pharmacodynamic response to anti platelet

regimen may be associated with cardiovascular, cerebrovascular events. The role of platelet

function testing to guide anti platelet therapy has been controversial. However updated American

and European practice guidelines have issued a Class 11b recommendation for platelet function

testing to facilitate the choice of anti-platelet regimen in high risk patients undergoing PCI such as

diabetes mellitus, diffuse three vessels coronary artery disease, left main stenosis, diffuse

atherosclerotic disease and chronic renal failure, and in patients with suspected pharmacodynamic

interaction with other drugs to assure the adequacy of platelet inhibition.

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351

STABLE ISCHEMIC HEART DISEASE: THE PRESENT AND THE FUTURE

M.S. Sidhu

Albany Medical Center, NY, USA

As has been well-established, patients with acute coronary syndromes, severe multi-vessel or left

main coronary artery disease, have better outcomes when prompt revascularization is performed

in addition to optimal medical therapy (OMT). However, in stable ischemic heart disease (SIHD)

patients, comparative effectiveness research has revealed equipoise between initial strategies of

OMT alone and OMT plus revascularization. Conducted in diverse SIHD patient populations and

throughout the spectrum of atherosclerotic and ischemic burden, the RITA-2, MASS II,

COURAGE, BARI 2D, and FAME 2 trials demonstrate that an initial conservative strategy of

OMT alone is associated with similar major cardiovascular outcomes (i.e., mortality, myocardial

infarction, or long-term angina relief), as with an initial invasive approach. What remains unclear

is whether there may be one or more subsets of patients with SIHD in whom revascularization may

be associated with a reduction in the rate of mortality or myocardial infarction, which is to be

addressed in the ongoing ISCHEMIA trial

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352

DECLINING TRENDS IN CARDIOGENIC SHOCK DEVELOPING DURING

HOSPITALIZATION FOR ACUTE MYOCARDIAL INFARCTION (AMI): INSIGHTS

FROM A POPULATION BASED CORONARY HEART DISEASE REGISTRY R. Makam, J. Gore, D. McManus, J. Yarzebski, R. Goldberg

University of Massachusetts Medical School, Worcester, MA, USA

Background: Cardiogenic shock (CS) is a serious and often fatal complication of AMI. The impact

of aggressive medical and procedural interventions for both prevention and management of CS

due to AMI is less clear, however. The purpose of the present study is to examine decade long

trends in the incidence and in-hospital death rates associated with CS that develops during

hospitalization for AMI as compared with CS that is present at the time of hospital admission.

Methods and Results: We studied 5,782 patients with AMI who were admitted to all 11 hospitals

in central MA on a biennial basis between 2001-2011 There was a marked decline in the frequency

of CS developing during hospitalization from 3.6% in 2001/2003 to 2.7% in 2009/2011 (p<0.05)

while the frequency of CS at admission did not change over time (1.5% in 2001/2003; 1.8% in

2009/2011). The in-hospital case fatality rate (CFR) among those who developed CS during

hospitalization declined from 47.1% in 2001/2003 to 28.6% in 2009/2011, whereas the hospital

CFRs associated with CS on admission worsened from 38.9% in 2001/2003 to 53.6% in

2009/2011

Conclusions: Over the past decade, significant declines have been observed in both the incidence

and in-hospital CFRs due to CS developing during AMI hospitalization. Early reperfusion and/or

revascularization interventions in patients hospitalized with AMI are potentially related to a

reduced incidence of CS developing during hospitalization for AMI, while the aggressive

management of CS which develops during hospitalization likely contributed to the improved short-

term survival of these high risk patients. The reasons for the stable incidence of CS that is present

on hospital admission and the worsening short term outcomes of these patients is less clear and

requires further examination

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364


HEART FAILURE: NOVEL RISK FACTORS, BIOMARKERS, NEW TREATMENT OPTIONS AND OUTCOME

353

RENAL BIOMARKERS PREDICT ADVERSE OUTCOMES IN HEART FAILURE

WITH PRESERVED EJECTION FRACTION A. Singh1, S. Lee1, P.J. Tan2, P. Huang2, Y. Cao1, C. Kam3, S.C. Chai1, T.S. Chee1,

K.L. Tong1, G. Leong1

1. Department of Cardiology, Changi General Hospital, Singapore, Singapore

2. Clinical Measurement Unit, Changi General Hospital, Singapore, Singapore

3. Clinical Trials & Research Unit, Changi General Hospital, Singapore, Singapore

Objectives: We sought to identify predictors of heart failure (HF) hospitalization in heart failure

with preserved ejection fraction (HFpEF) patients by evaluating biomarkers and transthoracic

echocardiogram (TTE) parameters.

Background: HFpEF is an increasingly recognised clinical entity that accounts for approximately

half of all HF diagnoses, yet remains challenging to prognosticate.

Methods: This was an observational prospective study of patients admitted in 2013 for HFpEF.

One-year follow-up data on HF admissions was obtained.

Results: Our HFpEF population (n=48) was 47.9% female, with a mean age of 71.9 ± 15.3 years.

Mean serum urea, creatinine, and estimated glomerular filtration rate (eGFR) were 13.9 ± 12.8

mmol/L, 185 ± 131.3 umol/L and 40.8 ± 27.2 ml/min per 1.73m2 respectively. Serum urea and

creatinine levels, along with a lower eGFR, correlated with more HF admissions (r=0.365 p=0.011,

r=0.411 p=0.004 and r=-0.452 p=0.001 respectively). The same biomarkers correlated with longer

hospital stays for HF (urea r=0.404 p=004, creatinine r=0.450 p=0.001 and eGFR r=-0.517

p<0.001). Predictably, higher serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels

and higher TTE ratio of mitral velocity to mitral annulus early diastolic velocity (E/E') also both

correlated with increased HF admissions (r=0.411, p=0.004 and r=0.463, p=0.001 respectively).

Patients' age, serum HbA1c and LDL-C levels showed no significant correlation with HF

hospitalization. Multiple regression analysis showed E/E', eGFR, NT-proBNP and age were all

statistically significant (p<0.05) predictors of HF admissions.

Conclusion: Renal biomarkers are useful prognostic factors in predicting readmissions for HFpEF,

along with the mainstays of serum NT-proBNP and E/E'.

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354

PREDICTORS OF RESPONSE IN PATIENTS WITH ACUTE DECOMPENSATED

HEART FAILURE REQUIRING MILRINONE J.L. Turner1, J.J. Teuteberg2, M.A. Mathier2, R. Ramani2, D. Ishizawar2, M.A. Simon2, D.

McNamara2, B.C. Lampert2

1. The Ohio State University, Columbus, OH, USA

2. University of Pittsburgh, Pittsburgh, PA, USA

Objectives: To determine predictors of improved short term clinical outcomes in decompensated

heart failure with reduced ejection fraction (HFrEF) requiring milrinone.

Background: Milrinone is a phosphodiesterase-3 inhibitor (PDE-3) which improves cardiac output

and hemodynamics in patients with decompensated HFrEF. Inotropes such as milrinone, however,

have been associated with increased mortality, and predictors of which patients may have the best

hemodynamic response are not clearly understood.

Methods: We prospectively observed 49 patients with decompensated HFrEF requiring milrinone.

Baseline clinical and hemodynamic parameters obtained at milrinone initiation were compared

using Pearson product-moment correlation coefficients with response to milrinone measured by

net 72 hour diuresis (72HD), length of inotrope use, and length of stay (LOS).

Results: Lower pulmonary artery saturation was associated with increased 72HD (R2=0.39,

p=0.03) but longer duration of inotrope use (R2=-0.50, p=0.003) and increased LOS (R2=-0.46,

p=0.008). Elevated right atrial pressure was associated with lower 72HD (R2=0.52, p=0.002) and

an increased LOS (R2=0.37, p=0.04). Increased serum creatinine (R2=0.40, p=0.005) and reduced

serum sodium (R2=0.38, p=0.007) were associated with increased LOS. Increased heart rate was

also associated with lower 72HD (R2=-0.33, p=0.02) and increased LOS (R2=0.33, p=0.02).

Chronic stable dose of outpatient beta-blocker, ejection fraction, and mean arterial pressure had

no significant correlation with outcomes.

Conclusions: Markers of advanced heart failure (elevated right atrial pressure, increased serum

creatinine, reduced serum sodium, increased heart rate) may predict resistance to milrinone. In

patients who present with these signs, close attention to inotrope resistance and early consideration

of mechanical circulatory support should be considered.

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355

CORRELATION BETWEEN AORTIC ROOT DILATION AND DIASTOLIC

DYSFUNCTION AND RELATIONSHIP WITH OTHER PARAMETERS P. Rodriguez-Lozano, S. Raslan, A. Melhem, M. Shieh, A. Khan, P. Nalabothu,

M. Morsy, W. Khalife, K. Sadat


Background: Consensus is lacking about the clinical importance of aortic root dilatation in

assessment of the risk of development of Diastolic Dysfunction (DD).

Objective: The aim of this study was to assess the aortic root dilatation in patients with Diastolic

Dysfunction (DD).

Methods: We retrospectively reviewed 2,262 medical records of patients receiving

Echocardiograms at a University hospital between 2008 year and 2012 year. The patients were

divided in two groups according to presence or absence of diastolic dysfunction. Aortic root

diameter was measured by M-mode echocardiography, and LV diastolic function was evaluated

by measuring the peak velocity of early (E) and late (A) diastolic transmitral blood flow, peak

early diastolic mitral annular velocity (E') by Tissue Doppler echocardiography, and pulmonary

venous sampling. Aortic dilation was assessed by measurement of aortic root diameter <3.7mm

vs. ≥ 3.7mm

Results: Bivariate analysis between Aortic dilation (AD) and DD showed that AD was present in

15.2% of patients with DD vs. 11.3% without DD (chi-square p= 0.0173). A multivariable logistic

regression analysis indicated that age (OR=1.041, 95% CI=1.014-1.068, p=0.0030) and

hypertension (OR=3.269, 95% CI=1.273-8.391, p=0.0138) were associated with the presence of

DD. None of the other predictor variables showed any statistically significant association (AO

dilation, Pro BNP, BMI and DM).

Conclusions: Aortic root dilation is strongly associated with DD in bivariate analyses, but this

association does not persist when entered into a model adjusting for other parameters.

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356

EFFECTS OF LIBERAL VERSUS RESTRICTIVE BLOOD TRANSFUSION

STRATEGIES IN CONGESTIVE HEART FAILURE

S.V. Patel1, P. Patel2, R. Minhasn3, M. Patel4, H. Gill1, P. Kaleka1, K. Waraich1

1. Department of Internal Medicine, Western Reserve Health Education, Youngstown, OH, USA

2. Medical College of Qingdao University, Shandong, China

3. American University of Antigua, Antigua and Barbuda

4. Christus Schumpert Highland Hospital, Shreveport, LA, USA

Objectives: The aim of this study was to ascertain proper use of blood transfusion in congestive

heart failure (CHF).

Background: Anemia is one of major comorbidities and an important prognostic factor, which is

almost 30% prevalent in CHF. Blood transfusion (BT) is primary standard of care for anemia. No

clear data is available regarding BT strategies in CHF regarding when to transfuse and what should

be the goal of hemoglobin (Hb).

Methods: We conducted a retrospective-chart review study in our hospital after obtaining IRB

approval. After excluding patients who had recent surgery, acute bleeding episode and acute

coronary event, we found 56 patients who received BT during in-patient hospital stay regarding

CHF. We divided them into 2 groups: Restrictive (RBT) vs Liberal (LBT) blood transfusion

strategies (12 vs 44 patients; Transfusion Hb threshold <7 vs <9 with a goal set >9 vs >10-12

gm/dl, respectively).

Results: The mean age of sample was 75 ± 2 years, 50% were females, and 54 % had chronic

kidney disease. Results shown in RBT vs LBT group, baseline Hb was 10.5 vs 10.6 gm/dl; numbers

of BT were used 2.4 vs 1.5 with p-value=0.003 and length of stay: <=12 days: 83% vs 50%; >12

days: 17% vs 50%; p-value=0.0131, respectively. No BT reactions were found in any patients.

Conclusions: We report significantly lower length of stay in RBT than LBT group. As this is a

small pilot study, we are suggesting a need for larger study to reproduce similar findings.

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357

PREDICTING READMISSION IN A HEART FAILURE POPULATION AT A RURAL

TERTIARY CARE HOSPITAL

D. Stapleton, H. Prasad, E. Stapleton, G. Choudhary, F. Ali

Guthrie Clinic/Robert Packer Hospital, Sayre, PA, USA

Background: Heart Failure (HF) remains the primary cause of admission to hospital in the United States.

Methods: 405 patients’ charts admitted with a diagnosis of acute systolic HF or acute on chronic systolic HF with a

LVEF ≤ 40%. 21 data elements from the medical record available at the time closest to the initial follow up visit were

abstracted. These data elements are as presented in tables I and II.

Scoring Equation for the Log Odds of 30-Day Readmission

Log Odds of 30-Day Readmission = -0.7193 – 0.0434 *Age + 0.0864*[maximum (0,Age-63)] + 0.0312*Weight –

0.0690*[maximum(0,Weight-95)] - 0.00795*Cholesterol + 0.0302*[maximum(0,Cholesterol-175)]

Results: Tables I and II report the descriptive statistics stratified by readmission status. One year all-cause mortality

rates were 19.5 % reflecting advanced heart failure population. Among all the variables analyzed, age (>63 yrs),

weight (< 95 kg), and total cholesterol (>175 mg/dl) were found to be associated with 30 day readmission. Patients in

the readmission groups were seen in outpatient clinic within 2 weeks from the discharge from the hospital.

Conclusion: In a rural tertiary care setting, these data suggest that the clinical milieu of older age, lower weight and

elevated cholesterol play a role in the risk of readmission for heart failure.

Table I: Descriptive Statistics by Readmission Status: Continuous Variables

Variable Readmission within

30 Days (n=92)

No Readmission within 30

Days (n=302)

P-Value

Age 75.3 (13.3) 73.5 (12.2) 0.0736

Weight (kg) 89.7 (15.0) 91.1 (25.6) 0.4043

EF 28.5 (9.2) 29.0 (9.4) 0.5419

SBP 122.7 (19.3) 121.4 (17.3) 0.8624

HG 12.0 (2.3) 12.2 (2.0) 0.4084

Total Cholesterol 150.4 (52.7) 144.9 (39.1) 0.9550

Creatinine 1.5 (0.8) 1.6 (0.9) 0.6003

NA 137.9 (4.7) 137.9 (4.0) 0.6733

K 4.3 (0.5) 4.3 (0.5) 0.4325

QRS 126.6 (36.6) 123.1 (37.1) 0.3761

Table II: Descriptive Statistics by Readmission Status: Categorical Variables

Variable Readmission within 30

days (n=92)

No Readmission within 30

Days (n=302)

P-value

Male 56 (60.9%) 184 (60.9) 0.9921

Ischemic 57 (62.0%) 206 (68.2%) 0.2648

ACEI/ARB 66 (71.7%) 231 (76.5%) 0.3544

Beta Blockers 81 (88.0%) 262 (86.8%) 0.7472

Statins 50 (54.4%) 183 (60.6%) 0.2858

Aldo Blocker 29 (31.5%) 93 (30.8%) 0.8949

Diuretics 75 (81.5%) 264 (87.4%) 0.1531

ICD 0.6614

No 45 (48.9%) 143 (47.3%)

Yes 18 (19.6%) 50 (16.6%)

BIV-ICD 0.7138

No 39 (42.4%) 117 (38.7%)

Yes 32 (34.8%) 104 (34.4%)

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358

FACTORS ASSOCIATED WITH HEART FAILURE READMISSIONS FROM

SKILLED NURSING FACILITIES

F.J. Akande

Stony Brook University, Stony Brook, NY, USA

Background: Despite guideline-driven pharmacological therapies and careful transitional care, the

rates of preventable hospital re-admission of heart failure patients and associated costs remain

unacceptably high in the SNF populations. Transfer to SNF is one strategy to limit hospitalizations.

As such, 25% of patients are still symptomatic at time of discharge.

Purpose: The objective of this study is to identify patient factors affecting re-admissions of HF

patients residing in SNF within 30-days.

Methods: A retrospective electronic chart review was completed on patients >65 years with HF

who were admitted into large medical center between 2012 and 2014. Descriptive statistics and

univariate analyses using the chi-square test or Fisher’s exact test for categorical variables and the

Mann-Whitney test for continuous data was used to compare patients readmitted within 30 days

vs. those who were not readmitted within 30 days. Significant factors associated with readmission

in the univariate analysis (p<0.10) were included for a multivariate logistic regression model. A

receiver operating characteristic (ROC) curve was constructed to look at the final model’s ability

to predict the outcome. A numerical measure of the accuracy of the model was obtained from the

area under the curve (AUC), where an area of 1.0 signifies near perfect accuracy. The analysis of

LOS was accomplished by applying standard methods of survival analysis, i.e., computing the

Kaplan-Meier product limit curves, where the data were stratified by readmission within 30 days

(Yes vs. No). No data were considered ‘censored’. The groups were compared using the log-rank

test. The median rates for each group were obtained from the Kaplan-Meier/Product-Limit

Estimates and their corresponding 95% confidence intervals were computed, using Greenwood’s

formula to calculate the standard error. Unless otherwise specified, a result was considered

statistically significant at the p<0.05 level of significance.

Results: Fifteen variables: creatinine, weight difference, CKD, Angina, Arrhythmia, VHD,

Tobacco, ADL, independent in bathing, independent in the toilet, S3 Heart sounds present, HJR,

AF, Nitrates, and Hydralazine, were identified for the multivariate logistic regression as potential

risk factors associated with “readmission within 30 days”. Based on 23 readmissions within 30

days, our final model included only 2 predictor variables. Creatinine and ADLs were included in

the final model as this subset of predictors was found to be the best for prediction of “readmission

within 30 days”. Creatinine (p<0.0087) and ADLs (p<0.0077) were both significantly associated

with readmission within 30 days in the final logistic regression model. Every 1-unit increase in

creatinine is associated with an 87% increase in the odds of being readmitted within 30 days (OR

= 1.87). Those patients who require assistance with ADLs are over 9 times more likely to be

readmitted within 30 days (OR=9.25) as compared to patients who are independent.

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359

DISCHARGE HOME HEALTH VS. HOSPICE REFERRAL AND 30-DAY ALL-CAUSE

READMISSION IN MEDICARE BENEFICIARIES HOSPITALIZED FOR HEART

FAILURE A. Ahmed, R.E. Kheirbek, R.D. Fletcher

VA Medical Center, Washington, DC, USA

Background: Heart failure (HF) is the leading cause for 30-day all-cause hospital readmission, a

target for reduction in the new U.S. healthcare reform law. Discharge hospice referral has been

shown to be associated with lower readmission. Sicker HF patients are often referred to home

health (HH) care. However, 30-day all-cause hospital readmission for patients receiving these two

referrals have not been compared before.

Methods: In the Alabama HF Project, of the 6549 HF patients who were discharged alive home,

129 received hospice referral and 1369 received HH referral during hospital discharge. Of the 1369

receiving HH referral, 359 died within six months after discharge and were considered hospice-

eligible. Thus, our pre-match cohort consisted 488 (129+359) patients. Propensity scores for

hospice referral were estimated for each of the 488 patients and were used to match 124 of the 129

patients in the hospice group with 124 patients in the HH group who had similar propensity scores,

thus assembling a matched cohort of 248 patients balanced on 22 baseline characteristics (mean

age, 79 years, 54% women and 19% African American).

Results: 30-day all-cause readmission occurred in 5% and 46% of matched patients receiving

discharge hospice and HH referrals, respectively (HR for hospice referral, 0.10; 95% CI, 0.04-

0.23). There was similar reduction in 30-day HF readmission (HR, 0.15; 95% CI, 0.05-0.44).

Although 30-day mortality was higher in the hospice group (44% vs. 32%; HR, 1.57; 95% CI,

1.05-2.36), it was similar at 90 days post-discharge (66% vs. 63%; HR, 1.10; 95% CI, 0.80-1.49).

Conclusions: Medicare beneficiaries hospitalized for HF receiving discharge hospice referral had

lower 30-day all-cause readmission rates than those receiving discharge home health referral that

died within 6 months of hospital discharge.

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360

READMISSIONS: HOW MANY ARE ACTUALLY PREVENTABLE? M. Farbaniec, T. Schmidt, P. Alagona, A. Foy

Penn State Hershey Medical Center, Hershey, PA, USA

Objective: To analyze 30 day readmission data for an acute cardiology service and determine the

percentage of preventable readmissions.

Introduction: Readmissions are an important issue for patients, physicians, payers, and

policymakers. The all-cause readmission rate in 2010 was about 19.2% among Medicare

beneficiaries costing the US economy approximately 17.5 billion dollars. Some believe the

majority of readmissions are preventable and thus, payers should penalize hospitals and providers

for readmission. However, root cause analyses of readmissions from the provider perspective have

not been performed. It may be unfair to penalize readmissions if the majority is not preventable.

Methods: Retrospective review of the electronic medical record was performed on all 30 day

readmissions where the index admission was on the acute cardiology service at a single, academic

medical center. The population was a total of 152 patients readmitted from 7/1/2013 – 11/16/14.

Root cause analysis was performed by two independent physicians and readmissions were deemed

‘preventable’, ‘maybe preventable’, or ‘not preventable’ based on review of the medical record.

Disagreements were settled by an additional reviewer and inter-rater agreement was determined

by a weighted kappa analysis.

Results: Of 152 readmissions, only 32 (21%) were considered ‘preventable’ or ‘maybe

preventable’. The reviewers agreed on 81.3% of cases and the weighted kappa was 0.41 indicating

moderate agreement. Fifty-nine (59%) of ‘preventable’ and ‘maybe preventable’ readmissions

were considered medication related and thirty-one (31%) were considered management related.

Conclusions: Preventable readmissions account for a small percentage of total readmissions.

Payment policies aimed at penalizing readmission are thus, unlikely to improve quality and may

disincentivize providers from appropriately readmitting patients for necessary and appropriate

medical care. Other mechanisms to reduce health care cost growth such as finding ways to reduce

preference-sensitive, low-value medical care would be more appropriate than penalizing providers

and hospitals for readmission.

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361

FRACTIONAL EXCRETION OF UREA AS A PROGNOSTIC INDICATOR IN

PATIENTS WITH LOW CARDIAC INDEX R.C. Liu, J. Chuang, M. Yeh

Beverly Hospital, Montebello, CA, USA

Background: There is a tremendous amount of difficulty in predicting which patients with acutely

decompensated heart failure will have a poor prognosis in the near future. None of the published

markers associated with advanced heart failure are very sensitive in their prognostic values. A

fractional excretion of urea is a measurement used by nephrologists to determine the state of renal

perfusion. We evaluated the prognostic value of the fractional excretion of urea in patients with

low cardiac indices.

Methods and Results: A retrospective chart review spanning 6 months was performed. Those

patients with low cardiac indices of less than 2L/min/m2 and had a fractional excretion of urea

measured during the hospitalization were analyzed. There was a 100% negative predictive value

(95% CI: 73.35-100%) associated with a normal fractional excretion of urea. The odds ratio of

having an adverse event associated with an abnormal fractional excretion of urea was 17.9 (95%

CI: 0.91-350.9, p-value=0.0578).

Conclusion: Based upon the results of this study, there is a suggestion that the fractional excretion

of urea can be a very sensitive prognostic indicator in patients with compromised cardiac function.

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DIABETES, HYPERTENSION AND CARDIOVASCULAR DISEASE – RISK AND MANAGEMENT

362

COMPARATIVE PROGNOSTIC VALUE OF DIFFERENT AMBULATORY BLOOD

PRESSURE PARAMETERS AS PREDICTORS OF STROKE: THE HYGIA PROJECT D.E. Ayala1, J.J. Crespo2, M. Dominguez-Sardina2, A. Moya3, A. Otero4, M.T. Rios2, M.C.

Castineira5, S.M. Gomara3, J.R. Fernandez1, R.C. Hermida1






Objectives: Several features of blood pressure (BP) patterning determined by ambulatory

monitoring (ABPM) have been explored as potential predictors of stroke. Some, but not all, studies

have concluded that elevated morning BP surge or increased BP variability might be significant

markers of stroke. We evaluated the comparative prognostic value for stroke of clinic BP and

multiple ABPM-derived characteristics, including asleep and awake BP means, morning surge,

and indices of BP variability among the participants in the Hygia Project, designed to evaluate

prospectively CVD risk by ABPM in primary care centers of Northwest Spain.

Methods: This study involved 11255 subjects, 6028 men/5227 women, 58.9±14.5 years of age,

prospectively evaluated throughout a 4.0-year median follow-up. BP was measured at 20-min

intervals from 07:00 to 23:00h and at 30-min intervals at night for 48h.

Results: We documented 147 ischemic and 29 hemorrhagic strokes. When each ABPM-derived

parameter was analyzed separately, the asleep systolic BP mean was the most significant predictor

of stroke (adjusted hazard ratio 1.35; 95%CI [1.20-1.52] for each 1-SD increase; P<0.001). A

greater morning BP surge was significantly associated with lower, not higher, stroke risk (0.87

[0.76-0.99], P=0.042). After adjustment by asleep systolic BP mean, neither clinic BP nor any

other ABPM-derived parameter, including awake and 48h means, sleep-time relative BP decline,

morning surge, and indices of awake, asleep and 24h BP variability, was significantly associated

with increased/decreased risk of stroke.

Conclusions: Progressively elevated sleep-time systolic BP mean is the only significant and

independent prognostic marker of stroke. Contrary to current believe, neither a greater morning

BP surge, morning hypertension, or extreme-dipper BP patterning increase the risk of stroke after

adjusting by asleep BP level. On the basis of the null prognostic value of clinic BP here

corroborated, ABPM should be considered a clinical requirement for proper risk stratification.

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363

FETUIN-B IMPAIRS CARDIAC INSULIN SIGNALING AND CONTRIBUTES TO

INCREASED CARDIAC ISCHEMIA/REPERFUSION INJURY SUSCEPTIBILITY IN

DIABETES W.Z. Wang, F. Fu, K. Wang, J.X. Sun, Z.W. Shi, X.Y. Liang, H.F. Zhang

Experiment Teaching Center, Fourth Military Medical University, Xi’an, China

Objectives: This study was aim to investigate the role of fetuin-B in diabetic myocardial

ischemia/reperfusion (MI/R) injury and its underlying mechanisms.

Background: Diabetes mellitus (DM) increases morbidity/mortality of ischemic heart disease.

Accumulating evidence suggests that elevated serum fetuin-A level causes impaired glycemic

control. However, the role of fetuin-A and its paraloguefetuin-B in diabetic MI/R injury is poorly

understood.

Methods: The high-fat diet-fed streptozotocin (HFD-STZ) diabetic mice weresubjected to MI/R.

In vitro, H9c2 cardiomyocytes were subjected to hypoxia/reoxygenation (H/R).

Results: Compared with the normal animals, diabeticmice showed more severe MI/R injury and

cardiac functional impairment. The diabetic heart exhibited increased fetuin-B (but not fetuin-A)

expression and impaired insulin signaling as evidenced by decreased insulin-stimulated threonine

phosphorylation of IRS-1 and reduced insulin-stimulated Akt phosphorylation and GLUT4

membrane translocation. Cardiac-specific knockdown of fetuin-Brestored cardiac insulin

signaling. Meanwhile, knocking down fetuin-Breduced MI/R injury in diabetic mice as evidenced

by decreased infarct size and increased cardiacfunction. Moreover, overexpression of fetuin-B in

H9c2 cardiomyocytes (adenoviral vector) impaired insulin signaling andincreased H/R injury

(cardiomyocyteapoptosis and viability). Increased fetuin-B expression was associated with

enhanced FoxO1 activation in diabetic hearts. ChIP showed that FoxO1 binds the fetuin-

Bpromoter. FoxO1 siRNA significantly decreased fetuin-B expression in diabetic mice.

Adenoviral vector-mediated overexpression of FoxO1 in H9c2 cardiomyocytesinduced increased

fetuin-B expression and blunted insulin signaling.

Conclusions: Our results demonstrate that increased fetuin-Bexpression induced by FoxO1

activation inhibits cardiac insulin signaling andrenders diabetic hearts more susceptible to MI/R

injury.

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364

MORNING SURGE AND SLEEP-TIME BLOOD PRESSURE AS PROGNOSTIC

MARKERS OF CARDIOVASCULAR RISK: THE HYGIA PROYECT R.C. Hermida1, M. Dominguez-Sardina2, A. Otero3, M.T. Rios2, S.M. Gomara4,

A. Moya6, M.C. Castineira5, A. Mojon1, J.R. Fernandez1, D.E. Ayala1






Objectives: The extent of blood pressure (BP) surge upon waking has been associated with

increased cardiovascular (CVD) risk in some, but not all, studies. Numerous studies, however,

have consistently shown the association between elevated sleep-time BP mean and the rising BP

pattern with markedly increased CVD risk, leading to a paradox, as patients with sleep-time

hypertension or non-dipper/riser BP pattern have attenuated morning BP surge.

Methods: This study involved 11255 subjects, 6028 men/5227 women, 58.9±14.5 years of age,

prospectively evaluated throughout a 4.0-year median follow-up. BP was measured at 20-min

intervals from 07:00 to 23:00h and at 30-min intervals at night for 48h.

Results: We documented 1539 total events, including 400 deaths, 176 strokes, 144 myocardial

infarctions, 147 coronary revascularizations, and 193 heart failures. A greater prewaking systolic

BP surge was associated with significantly lower, not higher, CVD risk in a Cox proportional-

hazard model adjusted for the significant influential characteristics of age, sex, diabetes, chronic

kidney disease, cigarette smoking, waist perimeter, and previous CVD event (hazard ratio [HR]

0.83 [95%CI 0.78-0.88] per each 1-SD increment; P<0.001). The HR was progressively and

significantly higher in the first three than in the last two quintiles of increasing prewaking BP

surge. The prognostic value of morning surge markedly decreased after correcting by the asleep

BP mean, the single most significant prognostic marked of total CVD events (HR=1.37 [1.29-

1.44], P<0.001).

Conclusions: Our findings document that, when properly analyzed as a continuous variable, a

larger morning BP surge is associated with a significantly lower CVD risk, in line with the

markedly greater risk associated with decreasing dipping of the BP pattern, and the most highly

significant prognostic value of progressively elevated asleep BP, an independent prognostic

marker of CVD risk that has also been prospectively validated as a relevant therapeutic target for

CVD risk reduction.

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365

PATIENT CHARACTERISTICS ASSOCIATED WITH OBESITY RELATED

HYPERTENSION IN OBESE AFRICAN AMERICANS AND HYPERTENSION NON

RESOLUTION AFTER BARIATRIC SURGERY: A SINGLE CENTER STUDY C. Gandotra, J.S. Ngwa, A. Mahajan, G. Ortega, C.C. Emenari, N.D. Molyneaux,

S.A. Layne, M. Turner, D. Tran, T.M. Fullum

Howard University Hospital, Washington DC, USA

Background: Obesity related hypertension (HTN) disproportionately affects African American

(AA) population, reversing the declining trend of cardiovascular morbidity and mortality. Rou-en-

Y gastric bypass (RYGB) surgery is the most effective bariatric surgery (BS) procedure to treat

obesity and obesity related hypertension. We examined the clinical characteristics associated with

obesity related HTN in an obese AA cohort presenting for BS and with one year HTN non

resolution in obese AA patients who underwent RYGB surgery at the Howard University Center

for Wellness and Weight Loss Surgery (HUCWWLS).

Methods: A retrospective review of a prospectively maintained database from January 2007

onwards at HUCWWLS was performed. Pre-operative clinical characteristics of obese AA

patients with HTN undergoing BS were compared. Also, patient characteristics associated with

one year HTN non resolution after RYGB were examined.

Results: Of 242 obese AA patients presenting for BS; 168 (69 %) had preoperative HTN. Patients

with preoperative HTN were older than patients without HTN (47 years vs. 38.5 years; p <.0001);

had higher prevalence of diabetes (45.83% vs. 9.46%; p <.0001) and dyslipidemia (42.3% vs. 10.8

%; p <.0001). In a subset of patients who underwent RYGB and had one year outcome data

available (n= 57), higher body mass index (BMI) and taking 2 or more HTN medications were

significantly associated with hypertension non resolution.

Conclusion: AA patients with obesity related hypertension presenting for BS are older; have higher

prevalence of diabetes and dyslipidemia irrespective of body mass index (BMI) compared to

normotensive AA obese patients. Obese AA hypertensive patients who have non resolution of

hypertension, 1 year after RYGB have higher BMI and are on 2 or more HTN medications.

Prospective studies are needed to further evaluate characteristics of obesity related HTN to guide

primary and secondary prevention strategies.

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366

PREVENTION A POSSIBLE DRUG–DRUG INTERACTION: IS CONCURRENT

ADMINISTRATION OF ORLISTAT AND PIOGLITAZONE INCREASE THE RISK OF

DRUG-INDUCED HEPATOTOXICITY? P. Rahimi-Moghaddam, M. Emzhik

Iran University of Medical Sciences, Tehran, Iran

Background: Drug–drug interactions (DDIs) are an emerging threat to public health and are

difficult to detect. To prevent DDIs and their burden, the possible DDIs should be kept in mind.

We know that obesity predisposes to the development of insulin resistance and type 2 diabetes as

well as heart disease. Therefore, combinational uses of anti-obesity drugs and glucose-lowering

drugs in a patient with cardiovascular problem are very common. As the hepatotoxicity of both

pioglitazone (an anti-diabetic drug) and orlistat (an anti-obesity drug) has been shown in some

cases, the aim of this study was to evaluate the interaction of pioglitazone and orlistat in human

hepatocellular cell line HepG2 cells to determine their effect on liver toxicity.

Methods: HepG2 cells were treated with 25 microM Pioglitazon (Pio), 20 microM Orlistat (Orl)

pioglitazone, orlistat or combination of them. The MTT assay was used to assess cell viability.

Results: Pioglitazone and orlistat combination caused a loss of HepG2 cell viability. While

pioglitazone (25 microM) and orliatat (20 microM) alone decreased the cell viability around 91%

and 85% respectively (not-significant, p > 0.05), the combination of these two drugs reduced the

amount of viable cells to 55% which was significant as compared by each drug alone. (p < 0.001).

Conclusions: Revealing the significant loss of viability of HepG2 cells in the combination use of

pioglitazone and orlistat indicates these two drugs should not be administered in the same time to

prevent their hepatotoxic effects especially in patients with liver dysfunction.

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MOLECULAR AND CELLULAR CARDIOLOGY, BASIC RESEARCH

367

MIR-210 SUPPRESSES GLUCOCORTICOID RECEPTOR IN RAT

CARDIOMYOCYTES IN RESPONSE TO FETAL HYPOXIA S.R. Martinez, C. Dasgupta, L. Zhang

Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA,

USA

Objective: To determine the role of hypoxia-induced micro-RNA (miR)-210 in the regulation of

glucocorticoid receptor (GR) in rat cardiomyocytes during fetal hypoxia.

Background: Studies by our lab and others have demonstrated that fetal hypoxia is a major

contributor to fetal programming of adult heart disease, and that glucocorticoids play a

cardioprotective role in adult rat ischemia/reperfusion injury. However, little is known concerning

the mechanisms by which fetal hypoxia influences glucocorticoid signaling. miR-210 is a well-

established hypoxia-sensitive miR that has been shown to modulate cardiomyocyte responses to

hypoxia. The role of miR-210 in the regulation of GR remains undetermined.

Methods: Cardiomyocytes were isolated from fetal (E21) rats and cultured under normoxia (21%

O2) or hypoxia (1% O2) for 24-48 hours. GR and nuclear HIF-1 alpha protein and GR mRNA

expression were measured using Western blot and qPCR, respectively. miR-210 expression,

measured using miScript qPCR, and GR protein levels were determined in the presence or absence

of a HIF-1 alpha inhibitor 2-methoxyestradiol (2ME). miR-210-mediated suppression of GR

expression was detected using a luciferase reporter assay. The miR-210 LNA-antimiR hsa-miR-

210-3p was used to confirm a causative role for miR-210 in the regulation of GR expression.

Results and Conclusions: Fetal cardiomyocytes exposed to hypoxia had significantly lower GR

protein, but not mRNA, expression. Nuclear HIF-1 alpha protein and miR-210 levels were

significantly increased in response to hypoxia; these effects were abrogated by exposure to 2ME

during hypoxia. miR-210 mimics suppressed GR expression through interaction with the 3’ UTR

of GR mRNA. Finally, hypoxia-induced reductions in GR were reversed by treatment with miR-

210 inhibitors during hypoxic insult. These results indicate that a HIF-1 alpha-mediated increase

in miR-210 plays a key role in hypoxia-induced reductions in GR expression in cardiomyocytes.

(Supported in part by NIH Grants HL118861 and HL118861S1)

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368

NEW VIEW OF THE CARDIAC RYANODINE RECEPTOR ARRANGEMENTS AND

THEIR FUNCTIONAL CORRELATION P. Asghari1, D.R. Scriven1, S. Sanatani2, S.K. Gandhi3, A.I. Campbell3, E.D. Moore1

1. Department of Cellular and Physiological Sciences, University of British Columbia,

Vancouver, BC, Canada

2. Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada

3. Department of Surgery, University of British Columbia, Vancouver, BC, Canada

Cardiac Ryanodine Receptor (RyR2) are integral membrane proteins that function as Calcium-

activated Calcium ion channels as well as a scaffold for a large number of signaling molecules that

modulate the release of Calcium through the channel. The relative position of the RyR2 tetramers

is therefore a critical determinant of their function. We have used transmission electron

tomography to map the position of the tetramers in myocytes sections and have used tissue

obtained from both rat and human hearts. Biochemical and physiological techniques were also

used to correlate structure with function. Dual-tilt electron tomography produced en face views of

both rat and human dyads, enabling a direct examination of RyR2 arrangement. Both species

showed that tetramer packing was non-uniform containing a mix of checkerboard and side-by-side

arrangements as well as isolated tetramers. We have shown that the tetramers’ arrangement

depended on the Magnesium concentration and on their phosphorylation status; in low Magnesium

and after phosphorylation RyR2s were positioned in largely checkerboard arrangements while in

response to high Magnesium the tetramers were positioned largely side by side. These tetramer

arrangements: side by side, mixed and checkerboard were associated with progressively increasing

Calcium spark frequencies. We have also shown that FK506-binding proteins, a well-known

regulators of RyR2, has a dramatic effect on tetramer arrangement. The correlation between

tetramer arrangement and spark frequency suggests that tetramer rearrangement may be another

mechanism whereby physiological processes operate and provides potential new mechanisms by

which the activity of RYR2, the dyad and cardiac contractility may be regulated.

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369

CORRELATION ANALYSIS OF THE ALTERATIONS IN EPOXY- AND HYDROXY-

ARACHIDONIC ACID METABOLITES WITH THE DEVELOPMENT OF CARDIAC

HYPERTROPHY IN RATS A.A. El-Sherbeni, A.O.S El-Kadi

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB,

Canada

Cardiac hypertrophy is an important risk factor for several heart diseases, most importantly heart

failure and sudden cardiac death. The importance of a group of arachidonic acids (AA) metabolites,

namely epoxy- and hydroxy-AA, has been reported during the development of cardiac

hypertrophy, though their specific roles are still unknown. In the current study, our aim was to

determine the association between epoxy- and hydroxy-AA and the alterations in heart dimensions

and functions, activation of fetal gene program and fibrotic and oxidative stress markers during

cardiac hypertrophy. Cardiac hypertrophy was developed in Sprague Dawley rats by inducing

pressure overload on the heart through aortic constriction procedure. Epoxy- and hydroxy-AA

formation during cardiac hypertrophy was measured by liquid chromatography-mass

spectrometry. Heart dimensions and functions were measured by echocardiography, while fetal

genes and fibrotic and oxidative stress markers were measured by real-time PCR. Pairwise

correlation analysis was performed, and univariate statistical analysis was used to identify

metabolites whose formation rate was statistically associated with each of the tested parameter.

Thereafter, non-parametric Spearman rank correlation coefficients were calculated. We found that

wall thickness and the decrease in heart volumes parameters were strongly correlated with epoxy-

AA and 5- and 9-hydroxy-AA (r=~0.75; p<0.001), while, 19-hydroxy-AA showed inverse

correlation (r=-0.42; p<0.01). Heart functions were not correlated with any of the tested

metabolites. In contrast, all metabolites, except 19-hydroxy-AA, showed a strong correlation with

fetal gene program activation, especially 8,9- and 11,12-epoxy-AA (r=~0.68; p<0.001). Fibrotic

and oxidative stress markers were better correlated with hydroxy-AA (r=~0.67; p<0.001), except

19-hydroxy-AA, compared with epoxy-AA (r=~0.51; p<0.05). In conclusion, the significant and

differential association between epoxy- and hydroxyl-AA and pathologies of cardiac hypertrophy

indicates the specific roles of these metabolites in the hypertrophic response of the heart to noxious

stimulus.

This work was supported by a grant from the CIHR to AOSE.

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370

IMPROVEMENT EFFECTS ON CARDIAC FUNCTION AFTER OSTEOPONTIN-

DERIVED SVVYGLR PEPTIDE-SECRETING MYOBLAST SHEETS

TRANSPLANTATION FOR ISCHEMIC CARDIOMYOPATHY A. Uchinaka1, Y. Hamada2, S. Mori2, N. Matsuura2, N. Kawaguchi1

1. Department of Cardiovascular Pathology, Osaka University Graduate School of Medicine,

Division of Health Sciences, Suita, Japan

2. Department of Molecular Pathology, Osaka University Graduate School of Medicine, Division

of Health Sciences, Suita, Japan

Autologous skeletal myoblasts sheet transplantation has the effect to secret cytokines that improve

heart function, and is applied in clinical practice as a successful therapy for failing hearts.

Osteopontin-derived seven-amino acid sequence (Ser-Val-Val-Tyr-Gly-Leu-Arg; SV peptide)

induces angiogenesis. In this study, we hypothesized that the gene modified functional myoblast

sheet could enhance therapeutic effect of sheet implantation and evaluated the long-term

therapeutic effects of SV peptide-secreting myoblast sheets in an ischemic cardiomyopathy model

rat. The ischemic cardiomyopathy model rats were divided into three groups: a WT-rSkMs group

(transplanted with wild-type myoblast sheets), a SV-rSkMs (transplanted with SV peptide-

secreting myoblast sheets); and a control group (ligation only). We evaluated cardiac function,

histological changes, and smooth muscle actin (SMA) expression via transforming growth factor

(TGF)-beta/Smad signaling. Cardiac function was significantly improved in the SV-rSkMs group.

The systolic function in the SV-rSkMs group especially showed a significant improvement. Left

ventricular remodeling was also significantly attenuated in the SV-rSkMs group. Furthermore,

many clusters of SMA-positive myofibroblasts were widely observed in the infarcted areas of the

SV-rSkMs group. In vitro, SMA expression was increased when the SV peptide was added to the

isolated cardiac fibroblasts (CFs). The SV peptide showed a high affinity for TGF-beta receptor,

and activated TGF-beta/Smad signaling on the CFs. SV peptide-secreting myoblast sheets

transplantation provided continuous improvement of cardiac function and left ventricular

remodeling. SV peptide induced myofibroblast differentiation of fibroblasts via TGF-beta/Smad

signaling, and increased muscle-like cells in infarcted area. The accumulation of SMA-positive

cells induced by SV peptide confers contractility to the stiff left ventricular wall. SV could possibly

be used as a new peptide drug for myocardial regeneration medicine and be expected future

usefulness for cardiac regeneration therapy without cell transplantation.

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MITOCHONDRIAL CALCIUM REGULATION FOR CARDIOPROTECTION J. Han, H.K. Kim, S.J. Noh, S.J. Lee, N. Kim, K.S. Ko, B.D. Rhee

Inje University, Busan, Korea

Preservation of mitochondrial function is essential to limit myocardial damage in ischaemic heart

disease. We examined the protective effects and mechanism of a new compound, NecroX-5, on

rat heart mitochondria in a hypoxia/reoxygenation (HR) model. NecroX-5 reduced mitochondrial

oxidative stress, prevented the collapse in mitochondrial membrane potential, improved

mitochondrial oxygen consumption, and suppressed mitochondrial Ca2+ overload during

reoxygenation in an in vitro rat heart HR model. Furthermore, NecroX-5 reduced the ouabain- or

histamine-induced increase in mitochondrial Ca2+. These findings suggest that NecroX-5 may act

as a mitochondrial Ca2+ uniporter inhibitor to protect cardiac mitochondria against HR damage.

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372

CARDIAC ENDOTHELIAL CELL-DERIVED EXOSOMES INDUCE SPECIFIC

REGULATORY B CELL J.P. Song, X. Chen, M.Y. Wang, Y. Xing, Z. Zheng, S.S. Hu

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for

Cardiovascular Diseases, Chinese Academy, China

The mechanism of immune tolerance is to be further understood. The present study aims to

investigate the role of the Cardiac endothelial cell (CEC)-derived exosomes in the induction of

regulatory B cells. In this study, CECs were isolated from the mouse heart. Exosomes were purified

from the culture supernatant of the primary endothelial cells. The suppressor functions of the

regulatory B cells were determined by flow cytometry. The results showed that the CEC-derived

exosomes carried integrin avb6. Exposure to lipopolysaccharide (LPS) induced B cells to express

the latent transforming growth factor (TGF)-b, the latter was converted to the active form, TGF-b,

by the exosome-derived avb6. The B cells released TGF-b in response to re-exposure to the

exosomes in the culture, which suppressed the effector T cell proliferation.

We conclude that CEC-derived exosomes have the capacity to induce B cells with immune

suppressor functions.

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VASCULAR BIOLOGY, BASIC AND TRANSLATIONAL RESEARCH

373

P66SHC-MEDIATES OXIDATIVE STRESS AND ENDOTHELIAL ACTIVATION

INDUCED BY MITOCHONDRIAL DYSFUNCTION IN HUVECS S.B. Jung, N. Harsha, J.B. Park, S.J. Choi, C.S. Kim

Chungnam National University, Daejeon, Korea

Mitochondrial dysfunction is the underlying mechanism involved in the pathophysiology of

various cardiovascular diseases like atherosclerosis. CRIF1 is a protein present in the mitochondria

associated with large mitoribosomal subunits, and CRIF1 knockdown induces mitochondrial

dysfunction and promotes ROS production. p66shc is a redox enzyme implicated in mitochondrial

ROS generation and translation of oxidative signals and, therefore, is a key factor for oxidative

stress in endothelial cells. In this study, we investigated whether mitochondrial dysfunction

induced by CRIF1 knockdown induces p66shc stimulation and plays any role in mitochondrial

dysfunction-induced endothelial activation. Knockdown of CRIF1 decreased the expression of

mitochondrial oxidative phosphorylation (OXPHOS) complexes I, III and IV, leading to increased

mitochondrial ROS (mtROS) and hyperpolarization of the mitochondrial membrane potential.

Knockdown of CRIF1 also stimulated phosphorylation of p66shc and increased cytosolic ROS in

endothelial cells. Furthermore, the expression of vascular cell adhesion molecule-1 and an

endoplasmic reticulum stress protein were increased upon CRIF1 knockdown in endothelial cells.

However, p66shc knockdown blunted the alteration in mitochondrial dynamics and ROS

production in CRIF1 knockdown endothelial cells. In addition, p66shc knockdown reduced the

CRIF1 knockdown-induced increases in adhesion between monocytes and endothelial cells. Taken

together, these results suggest that CRIF1 knockdown partially induces endothelial activation via

increased ROS production and phosphorylation of p66shc.

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374

ANTI-INFLAMMATORY FUNCTION OF APE1/REF-1 IN ENDOTHELIAL

ACTIVATION B.H. Jeon, H.K. Joo, S. Choi, Y.R. Lee, G. Kang, C.S. Kim

Research Institute of Medical Sciences, Chungnam National University, Daejeon, and

Department of Physiology, College of Medicine, Chungnam National University, Daejeon,

Korea

Apurinic apyrimidinic endonuclease 1/Redox factor-1 (APE1/Ref-1) has a pleiotropic role in

controlling cellular response to oxidative stress. APE1/Ref-1 is mainly localized in the nucleus,

but cytoplasmic localization has also been reported. A trafficking of APE1/Ref-1 between cellular

compartments is reflected to different types of stressors. N-terminal region contains the redox

regulatory domain characterized by 2 critical cysteine residues, C65 and C93. However, the

functional role of cytoplasmic APE1/Ref-1 and redox mutants (C65A/C93A) are still unknown.

We investigated the role of APE1/Ref-1 or its mutants on tumor necrosis factor-alpha(TNF-alpha)-

induced vascular cell adhesion molecule-1 (VCAM-1) expressions in endothelial cells. N-terminus

deletion mutants (putative nuclear localization signals) of APE1/Ref-1 were generated by deleting

28 amino acids of the N-terminus (29–318). The exposure of TNF-alpha increased the cytoplasmic

APE1/Ref-1, which was inhibited by NADPH oxidase inhibitor, not cycloheximide nor

leptomycin, suggesting cytoplasmic translocations of APE1/Ref-1. Transfection of an N-terminus

deletion mutant APE1/Ref-1(29-318) inhibited TNF-alpha-induced VCAM-1 expression,

indicating an anti-inflammatory role for APE1/Ref-1 in the cytoplasm. In contrast, redox mutant

of APE1/Ref-1 (C65A/C93A) transfection led to increased TNF-alpha-induced VCAM-1

expression. Our findings suggest cytoplasmic APE1/Ref-1 localization and redox cysteine residues

of APE1/Ref-1 are involved in critical role for anti-inflammatory activity of APE1/Ref-1 in

endothelial cells.

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375

HPLC-FLUORESCENCE METHOD FOR THE ENANTIOSELECTIVE ANALYSIS OF

PROPRANOLOL IN RAT SERUM USING IMMOBILIZED POLYSACCHARIDE-

BASED CHIRAL STATIONARY PHASE

A.K AL-Suwailem

Prince Sultan Cardiac Center, Riyadh, Kingdom of Saudi Arabia

A stereoselective high-performance liquid chromatographic (HPLC) method was developed and

validated to determine S-(−)- and R-(+)-propranolol in rat serum. Enantiomeric resolution was

achieved on cellulose tris(3,5-dimethylphenylcarbamate) immobilized onto spherical porous silica

chiral stationary phase (CSP) known as Chiralpak. A simple analytical method was validated using

a mobile phase consisted of n-hexane-ethanol-triethylamine (95:5:0.4%, v/v/v) at a flow rate of

0.6 mL min-1 and fluorescence detection set at excitation/emission wavelengths 290/375 nm. The

calibration curves were linear over the range of 10–400 ng mL-1 (R = 0.999) for each enantiomer

with a detection limit of 3 ng mL-1. The proposed method was validated in compliance with ICH

guidelines in terms of linearity, accuracy, precision, limits of detection and quantitation, and other

aspects of analytical validation. Actual quantification could be made for propranolol isomers in

serum obtained from rats that had been intraperitoneally (i.p.) administered a single dose of the

drug. The proposed method established in this study is simple and sensitive enough to be adopted

in the fields of clinical and forensic toxicology. Molecular modeling studies including energy

minimization and docking studies were first performed to illustrate the mechanism by which the

active enantiomer binds to the βeta-adrenergic receptor and second to find a suitable interpretation

of how both enantiomers are interacting with cellulose tris(3,5-dimethylphenylcarbamate) CSP

during the process of resolution. The latter interaction was demonstrated by calculating the binding

affinities and interaction distances between propranolol enantiomers and chiral selector.

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PROGRESS IN ECHOCARDIOGRAPHY

376

SPECKLE TRACKING ECHOCARDIOGRAPHY IN THE ASSESSMENT OF

CONSTRICTIVE PERICARDITIS L. Capotosto, R. Ashurov, F. Massoni, G. Placanica, S. Ricci, A. Vitarelli

Sapienza University, Cardiology and Medicine Depts, Rome, Italy

Background: The aim of the present study was to assess the incremental value of Speckle Tracking

Echocardiography (STE) for differentiation between CP and RCM. Although normal or

exaggerated early diastolic mitral annular velocity provides high specificity for differentiating

constrictive pericarditis (CP) from restrictive cardiomyopathy (RCM), its sensitivity has been

shown to be lower.

Methods: Twelve patients with CP, 8 with RCM, and 12 healthy controls were studied. Standard

mitral inflow Doppler and tissue Doppler echocardiography (TDI) were performed. LV TDI

annular peak systolic and diastolic velocities (S’, E’) and time difference between onset of mitral

inflow (E velocity) and onset of E' (E'-E time) were measured. LV longitudinal strain and systolic

and diastolic strain rate were obtained in the basal, mid and apical segments of septal and lateral

walls in apical 4-chamber view both by STE. Circumferential and radial strain and averaged LV

rotation and rotational velocities from the base and apex were also obtained by STE.

Results: E' and S' were significantly higher in patients with CP than RCM (9.1 ± 1.4 vs 4.4 ±

1.6cm/s, and 7.8 ± 1.2 vs 4.2 ± 1.4cm/s respectively, p <0.001). E'-E was significantly shorter in

patients with CP (25.8 ± 21.6 vs 56.5 ± 24.4ms, p <0.005). Impairment of longitudinal strain in

the antero-lateral wall (ALWLS) was shown in CP patients compared to controls (-14.2 ± 2.9 vs -

20.1 ± 2.8%, p<0.001) whereas circumferential and radial strain values did not change

significantly. ROC curves suggested that the thresholds offering an adequate compromise between

sensitivity and specificity for detection of CP were -15.2% for ALWLS (AUC 0.87), 32.8 ms for

E’-E time (AUC 0.78), and -5.1 cm/sec for E’ velocity (AUC 0.72).

Conclusions: STE indices provide incremental diagnostic information to conventional Doppler

echocardiography and can be helpful to differentiate between CP and RCM.

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377

ATRIAL FLUTTER HAS LESS SPONTANEOUS ECHO CONTRAST AND HIGHER

APPENDAGE EMPTYING VELOCITY THAN ATRIAL FIBRILLATION J.J. Huang, S. Reddy, T.H. Truong, P. Suryanarayana, S. McNitt, J.S. Alpert

University of Arizona Medical Center Tucson, AZ, USA

Objectives: We hypothesized that patients with atrial flutter (AFl) would have less incidence of

thrombus formation and better prognostic indicators of thromboembolism risk than patients with

atrial fibrillation (AF) on trans-esophageal echocardiography (TEE).

Background: The risk of stroke and thromboembolism in AF is established. The risk in patients

with atrial flutter AFl is not as evident.

Methods: A retrospective analysis of 1,800 patients undergoing TEE was performed. Those with

AF or AFl were reviewed. Exclusion criteria were chronic anticoagulation, prosthetic valve, mitral

valve disease, congenital heart disease and heart transplantation. 73 with AF and 38 with AFl were

included in the analysis. Patient demographics and TEEs were reviewed to obtain the data.

Results: Eight patients with thrombus were observed in the AF versus none in the AFl group,

which was statistically significant (p=0.05). The prevalence of spontaneous contrast and LAAEV

was significantly lower in AFl group (p <0.001). No spontaneous contrast was seen with LAAEV

>60 cm/sec. All eight patients with thrombi in the AF group had spontaneous contrast.

Conclusion: Patients with AFl have lower incidence of LAA thrombi, higher LAAEV and less

spontaneous contrast compared with AF patients, suggesting a lower risk for arterial

thromboembolism in AFl patients.

Atrial fibrillation

(n=73)

Atrial flutter

(n=38)

P value

Age (mean years) 63 63 0.890

Sex (female) 17/ 73 (23%) 8/38 (21%) 1.00

LVEF (mean%) 50.6 55.2 0.08

LAVI (mean) 31.6 29.8 0.257

Presence of Thrombus 8/73 (11%) 0/38 (0%) 0.05

Presence of Spontaneous contrast 38/73(52%) 5/38 (13%) <0.001

LAAEV (mean) 44.11 cm/sec 62.02 cm/sec <0.001

CHADS2 score 1.30 1.19 0.78

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378

THREE-DIMENSIONAL SPECKLE TRACKING ECHOCARDIOGRAPHY IN THE

ASSESSMENT OF RIGHT VENTRICULAR DYSFUNCTION AFTER SURGICAL

REPAIR OF TETRALOGY OF FALLOT L. Capotosto, I. D'Angeli, R. Ashurov, F. Miraldi, A. Vitarelli

Sapienza University, Cardiac Dept., Rome, Italy

Background: The combined effects of preoperative hypertrophy and hypoxia, possible

intraoperative myocardial damage, type of reconstruction, and acquired postoperative lesions such

as pulmonary regurgitation may result in impaired RV deformation in post-operative tetralogy of

Fallot (TF). Recently 3D speckle tracking echocardiography (3DSTE) has been proposed to assess

mechanical dyssynchrony in these patients but the role of electromechanical dysfunction is not

completely clear.

Methods: Sixteen patients after TF repair (aged 17-53years) with dilated right ventricle, right

bundle branch block (QRS >120ms), and NYHA class I or greater were studied with two-

dimensional and three-dimensional speckle tracking echocardiography. Right ventricular end-

diastolic and end-systolic volumes were measured from three-dimensional datasets and right

ventricular ejection fraction (3D-RVEF) was obtained. Right intraventricular dyssynchrony was

determined as the difference between the longest and shortest electromechanical coupling times in

the basal septal and lateral RV segments. Interventricular dyssynchrony was determined as the

difference between electromechanical coupling times in the basal lateral LV segment and the most

delayed RV segment. Sixteeen age-matched healthy subjects were selected as controls.

Results: Right intraventricular dyssynchrony (77.1+/-24.2ms vs 13.1+/-8.9ms) and

interventricular dyssynchrony (74.7+/-22.2ms vs 11.4+/-7.9ms) were shown in patients compared

to normal controls. Right intraventricular dyssynchrony correlated with RV longitudinal strain

(r=0.62, p<0.005), 3D RV end-systolic volume (r=0.47, p=0.02), and QRS duration (r=0.39,

p=0.03). Interventricular dyssynchrony correlated with RV longitudinal strain (r=0.73, p<0.001),

RV systolic pressure (r=0.59, p<0.005), 3D-RVEF (r=0.53, p=0.003), and QRS duration (r=-0.44,

p=0.031). Reduced RV strain, 3D-RVEF and prolonged QRS duration were the main determinant

factors predicting RV dyssynchrony by multivariate analysis. On ROC curves RV strain and 3D-

RVEF had optimal predictive accuracy of the NYHA functional class and a larger area under the

receiver operating characteristic curve than the QRS duration.

Conclusions: In patients with repaired TF RV dyssynchrony is associated with reduced 3D-RVEF

and RV 3DSTE parameters.

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379

DOBUTAMINE-INDUCED ATRIAL FIBRILLATION DURING DOBUTAMINE

STRESS ECHOCARDIOGRAPHY A. Sinha, Y. Acharaya, J. Bhattarai, R. Kumar, J. Shirani

Saint Luke’s University Hospital, Bethlehem, PA, USA

Objective and background: Endogenous catecholamines are implicates in initiation and

maintenance of atrial fibrillation (AF). Synthetic catecholamines have also been rare inducers of

AF.

The aim of this study was to determine the incidence and predictors of AF induced during

dobutamine stress echocardiography (DSE) as reported in English literature.

Methods and Results: A total of 27 studies including 51,972 patients reported the incidence of AF

during DSE from 1991 to 2011. The incidence of AF during DSE ranged from 0.3% to 2.2% (mean

0.9%). The dose of dobutamine used in these studies ranged from an initial dose of 2.5 to a peak

dose of 50 microgram/kg/min usually in graded 3 or 5-minute stages. Three studies used an

accelerated protocol for dobutamine infusion (fixed dose of 50 microgram/kg/min in 2 and two

fixed doses of 20 and 40 microgram/kg/min in another). Intravenous atropine was included in DSE

protocol in 24 (89%) studies with highest dose of 0.4 mg in 1, 1 mg in 15 and 2 mg in 8 studies.

Independent predictors of dobutamine-induced AF were reported in only 3 studies (n=21,394,

incidence of AF 1-1.9%) with a prior history of AF being the only consistently reported predictor

(odds ratio for development of AF up to 3.7).

Conclusion: AF is a rare complication of DSE and occurs more frequently in those with prior

history of AF.

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380

CORRELATE OF GLOBAL LONGITUDINAL, RADIAL AND AREA STRAIN IN

SEVERE AORTIC STENOSIS WITH NORMAL LEFT VENTRICULAR EJECTION

FRACTION: A THREE-DIMENSIONAL AND TWO-DIMENSIONAL MULTILAYER

SPECKLE TRACKING ECHOCARDIOGRAPHY E.J. Cho1, S.J. Park1, H.L. Yun1, H.J. Lim1, S.C. Lee1, D.J. Choi2, S.W. Park1



Background: The aim of this study was to the capability of real-time three-dimensional

echocardiography (RT3DE) and two-dimensional multilayer speckle-tracking

echocardiography(MSTE) in characterizing early abnormalities of left ventricular (LV) structure

and function in patients with severe aortic stenosis (AS) and normal LV ejection fraction

(EF±50%).

Methods: Conventional, 3D STE and MSTE were performed in 51 patients (mean age 68.9±9.0

yrs) with severe AS (aortic valve area <1 cm2, AV Vmax >4 m/sec or mean PG >40mmHg) and

normal LVEF but without overt coronary artery and 64 healthy controls. Global longitudinal strain

(GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain

(GRS) were calculated by RT3DE and MSTE.

Results: Severe AS group had lower 3D GLS, GAS and 2D epicardium, midwall and endocardium

GLS compared controls. But, 3D GCS, GRS was not significantly different between two groups.

In MSTE analysis, 2D LS and CS values decreased from the endocardial layer toward the

epicardial layer.

Conclusions: Three-dimensional and multilayer STE identifies early functional LV changes in

severe AS patients with normal LVEF. GLS and GAS impaired, while circumferential strain is

still preserved, supporting a normal LV chamber systolic function. Therefore, 3D and multilayer

STE may give additional information in the decision-making process for severe AS patients with

normal left ventricular function.

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381

PROGNOSTIC IMPLICATIONS OF RACE IN PATIENTS WITH NORMAL

DOBUTAMINE STRESS ECHO Y. Zheng, S. Siniara, R. Ferguson, Y. Chia, H. Lawson, S. Bulugahapitiya

Bradford Royal Infirmary, Bradford, West Yorkshire, UK

Aim: Stress Echo is an effective investigative tool to assess coronary artery disease. Given the

different risk factor profile for coronary artery disease between Asian and Caucasian populations,

the aim of this study was to assess whether there was a difference in prognostic outcome of a

normal Dobutamine stress echo (DSE) between the two population cohorts.

Method: A retrospective analysis was carried out on all patients that received a DSE between the

periods of April 2011 to December 2012. The echo results, patient letters and patient information

from a national electronic patient data system (System One) were reviewed retrospectively to

collect demographic, morbidity and mortality data.

Results: 211 patients were identified as having had a normal DSE. 61 patients were Asian in

origin and 148 were Caucasian with 2 described as another race. In this group, there were no

cardiac mortalities within the year. In the One year period 5 Non ST elevation myocardial

infarctions (NSTEMI’s) occurred giving a cardiac event rate of 23 per 1000 patients. Of these

NSTEMI patients 1 (1.6%) was Asian and 4 (2.7%) patients were Caucasian (p value=1.00).

Conclusion:

1. A normal DSE confers a good one year prognostic outcome in terms of cardiac mortality

and morbidity.

2. There is no difference in prognostic outcome of a normal DSE between the Asian and

Caucasian population.

3. Larger sample studies are required to confirm these findings.

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382

CORRELATION BETWEEN CARDIOVASCULAR AND LIVER MAGNETIC

RESONANCE T2* AND TRANSTHORACIC ECHOCARDIOGRAPHIC STUDY IN

THALASSEMIA PATIENTS M. Parsaee1, N. Akiash2, A. Azarkeivan3, Z. Ojaghi Haghighi1, M. Maleki4,

S.M.H. Adel2

1. Echocardiography Research Center, Rajaie Cardiovascular Medical and Research Center, Iran

University of Medical Sciences, Tehran, Iran

2. Atherosclerosis Research Center, Jundishapur University of Medical Sciences, Ahwaz, Iran

3. Transfusion Research center, High Institute for Research and Education in Transfusion

Medicine, Tehran, Iran

4. Cardiovascular Intervention Research Center, Rajaie Cardiovascular Medical and Research

Center, Iran University of Medical Sciences, Tehran, Iran

Background and Objective: Heart failure is the most important reason of mortality and morbidity

in thalassemia patients. Repeated blood transfusions, peripheral hemolysis and increased iron

absorption from intestinal tissue in thalassemia patients resulting iron overload and accumulation

of iron in tissues such as myocardium. Early detection of cardiac involvement is important to

improvement of prognosis in these patients. Transthoracic Echocardiography has been known as

a non-invasive technique for routine cardiac evaluation in thalassemia but left ventricular systolic

function remains approximately normal until late in thalassemia.

Method: 130 thalassemia patients (38.5% intermedia, 61.5% major) were selected, 8 patient were

excluded due to poor image quality in echocardiographic study. T2* cardiovascular and liver

magnetic resonance was performed in the patients to assessment of liver and myocardial iron load.

2D and 3D echocardiography and tissue Doppler study were performed on all subjects.

Results: The mean value of LVEF in the thalassemia patients were 60% ± 0.6%. PAP was higher

in thalassemia intermedia than thalassemia major (P = 0.014) and PAP correlated positively with

age (P=0.003). There was a significant correlation between longitudinal global strain and MRI T2*

of the liver (P = 0.02) and cardiac (P = 0.006). There was significant correlation between LVEF

(by 3D method) and cardiac MRI T2*(P = 0.05).

Conclusions: Thalassemia patients with cardiac and liver iron overload had lower longitudinal

global strain and LVEF therefore in unequipped centers which CMR is not available, evaluation

of longitudinal global strain and LVEF with 3dimentional method can be replacing tools.

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383

IS THERE ANY CORRELATION BETWEEN CHA2DS2-VASC SCORE TO LEFT

ATRIAL VOLUME INDEX? H.N. Patel, N.T. Nazir, C.J. Bai, A. Volgman

Rush University Medical Center, Chicago, IL, USA

Background: Current guidelines recommend use of CHA2DS2-VASC score for risk stratification

in prevention of thromboembolic events in patients with nonvalvular atrial fibrillation (AF). Left

atrial dysfunction can increase the risk of thrombus formation in the left atrium and left atrial

appendage, with left atrial remodeling and distortion as a precipitant for AF. Left atrial volume

index (LAVI) has also been shown to predict strokes and mortality in non-AF patients. We sought

to determine if there is any correlation between CHA2DS2-VASC score and LAVI.

Methods: A total of 813 patients were evaluated from June 2013 to June 2014; 207 patients met

inclusion criteria for diagnosis of AF and had echocardiographic data for calculation of LAVI.

Results: Of the cohort, 47% (n=96) were female and 53% (n=111) were male, mean age of 71.39

±11.91 years. The average CHA2DS2-VASC score was 4.56± 1.94. The mean LAVI was 36.68

±7.36. The figure shows lack of correlation between the 2 clinical factors.

Conclusion: Although CHA2DS2-VASC score and LAVI have both been shown to predict

strokes, we found no correlation in this observational study. Clinical risk factors and

echocardiographic features are independent predictors and are both useful for predicting

thromboembolic events in patients with AF.

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384

MAKING NOT-SO-OBVIOUS OBVIOUS; THE ROLE OF 2D ECHOCARDIOGRAPHY

IN DIAGNOSIS OF AORTIC DISSECTION S. Neupane, H. Othman, G.I. Cohen

St John Hospital and Medical Center, Detroit, MI, USA

Clinical presentation

Case 1: A 52 year old female with history of hypertension (HTN) presented with left sided neck

pain radiating to left jaw which resolved spontaneously. It was associated with transient difficulty

in speech. Physical examination was unremarkable. After a negative CT scan of head, she was

admitted. Transthoracic Echocardiogram (TTE) done for stroke workup showed dilated ascending

aorta with dissecting flap extending from aortic root to the arch with mild aortic regurgitation. CT

angiogram confirmed the findings of type A aortic dissection (AD). She underwent emergent

surgery and recovered well.

Case 2: A 66 year old male with history of HTN presented with sudden onset chest pain. He was

hypotensive and tachycardic at presentation. Cardiovascular exam revealed grade 2/6 diastolic

murmur. EKG showed ST depression in anterolateral leads with ST elevation in AVR and V1.

TTE performed prior to the transfer to cardiac catheterization lab showed dilatation of aortic root

and ascending aorta with large intimal flap prolapsing into the left ventricle outflow tract during

diastole with severe aortic regurgitation. CT angiogram confirmed the diagnosis of type A AD.

Despite undergoing emergent surgery, his clinical status continued to worsen and died.

Clinical significance: The role of TTE is somewhat limited in diagnosis of AD. It has high positive

predictive value, but it may be difficult to exclude the diagnosis if findings are negative. These

two cases illustrate the role of TTE as a quick useful tool in diagnosis of aortic dissection in near

miss scenarios.

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385

RUPTURED CASEOUS MITRAL ANNULAR CALCIFICATION PRESENTING AS A

MOBILE MASS R. Manikat1, F. Elmi1, .J Shirani2

1. Easton Hospital, Easton, PA, USA

2. St. Luke's University Hospital, Bethlehem, PA

Introduction: The annulus of the mitral valve commonly becomes calcified in the elderly. Mitral

valve annulus calcification (MAC) may be found in 10% of old patients and 40% of patients with

end-stage renal disease (ESRD) referred for echocardiography. Caseous calcification of the mitral

annulus (CCMA) may present as large intracavitary mass. Rupture of MAC has been reported as

a fatal complication of transapical aortic valve implantation. We report a case of spontaneous

rupture of mitral valve annular calcium with systemic embolism.

Case: A 63-year-old diabetic female with ESRD presented with purulent drainage from her left

foot. Wound culture showed a rare strain of Enterococcus and ceftazoline was started. ECG and

blood cultures were essentially unremarkable. MRI of the left foot showed no osteomyelitis or

cellulitis. Transthoracic and transesophageal echocardiography showed a mobile echodensity

measuring 0.9 x 0.6 cm attached to the atrial aspect of the posterior mitral valve annulus without

any valve dysfunction. Abdominal aortography with runoff showed severe diffuse atherosclerosis

involving distal vessels without evidence obvious evidence for thromboembolism. The patient was

started on anticoagulation and will be followed up for further imaging and management.

Discussion: CCMA is an unfamiliar condition with a generally benign course and potential for

rupture with complicating mitral valve dysfunction, conduction abnormalities and systemic

embolization. It is unclear whether interventions aimed at lowering mechanical shear forces (beta-

blockade), stabilizing atherosclerotic lesions (statins), or reducing phosphate overload would

prevent this particular complication of CCMAC.

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ATRIAL FIBRILLATION: DIAGNOSTIC ELECTROPHYSIOLOGY, ABLATION AND STROKE PREVENTION

386

CONTRIBUTION OF EPICARDIAL ADIPOSE TISSUE TO ATRIAL FIBRILLATION

SUBSTRATE WITH HIGH DOMINANT FREQUENCY IN ABLATION K. Kumagai, D. Kutsuzawa, K. Minami, Y. Yamaguchi, Y. Sugai, S. Oshima

Division of Cardiology, Gunma Prefectural Cardiovascular Center, Maebashi, Japan

Background: The peri-atrial epicardial adipose tissue (EAT) volume predicts the development of

new-onset atrial fibrillation (AF), and is associated with the severity of AF. EAT is associated with

the outcome after AF ablation. EAT is considered to induce electrical and structural remodeling

of the atrium leading to AF. EAT is located adjacent to high dominant frequency (DF) sites. The

relationship between the EAT location and efficacy of a combined high DF site and continuous

complex fractionated activation electrogram (CFAE) site ablation is unclear.

Methods: Fifty-five non-paroxysmal AF patients (26 persistent and 29 longstanding) underwent

pulmonary vein isolation (PVI) followed by a high DF site and continuous CFAE site ablation.

High DF sites (DF ≥8Hz) and continuous CFAE sites (fractionated intervals ≤50ms) were targeted.

The patients were divided into an AF-free group and AF-recurrent group.

Results: The AF freedom on antiarrhythmic drugs in persistent and longstanding persistent AF

patients was 88.5% and 75.9% over a 12-month follow-up period, respectively. The total EAT,

left atrial (LA)-EAT, and right atrial (RA)-EAT volumes did not indicate significant differences

between the AF-free and AF-recurrent groups. In the LA, the overlap between the high DF sites

and EAT was larger in the AF-free group than in the AF-recurrent group (57.0±33.3% vs.

22.6±23.3%, p<0.01). However, this overlap did not differ between the AF-free and AF-recurrent

groups in the RA (20.4±28.2% vs. 19.0±24.4%, NS). The overlap between the continuous CFAE

sites and EAT did not differ between the two groups in both the LA and RA. In addition, the

overlap between the AF substrate and EAT did not differ between the persistent AF and

longstanding persistent AF patients.

Conclusions: High DF sites that overlap with EAT may be important sources of AF.

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387

EFFECT OF AMIODARONE-WARFARIN INTERACTION ON ANTICOAGULATION

QUALITY IN A SINGLE CENTER R.D. White, K.W. Riggs, E.J. Ege, G.F. Petroski, S.M. Koerber, G. Flaker

University of Missouri School of Medicine, Columbia, MO, USA

Background: Clinical trials have reported a low time in therapeutic range (TTR) in patients with

atrial fibrillation treated with both warfarin and amiodarone. These trials included centers and

countries with both high and low TTR’s.

Objectives: To determine the impact of amiodarone on the TTR in a single, high-quality

anticoagulation clinic.

Methods: TTR was assessed in amiodarone and non-amiodarone treated patients from a University

Anticoagulation Clinic.

Results: Baseline characteristics between patients ever-taking or never-taking amiodarone were

similar, except more amiodarone patients were smokers (19.5% vs. 6.1%, p=0.0031). The TTR

calculated from 8,901 international normalized ratios (INR) in 249 non-amiodarone patients with

a mean follow-up of 34 +/- 20 months (mean 36 +/- 18 INR’s) was 66% +/- 16.6 compared with

61.3% +/- 16.2 (p=0.111) from 1,455 INR’s in 41 amiodarone treated patients with a mean follow-

up of 28 +/- 20 months (mean 35 +/- 22 INR’s). Factors associated with a low TTR were male

gender (p=0.0013), smoker (p=0.0048), and amiodarone use (p=0.0374). A second on-treatment

analysis, in which the TTR was calculated only during amiodarone therapy, resulted in similar

findings, however amiodarone did not emerge as a predictor of a low TTR. In 11 patients, the

TTR prior to amiodarone (54.5% +/- 22.2) was not significantly different in the first 3 months

(54.6% +/- 33.4) or after 3 months (67.2% +/- 33.7) of amiodarone.

Conclusion: In a single high-quality anticoagulation center, anticoagulation quality, as measured

by the TTR, can be comparable in amiodarone and non-amiodarone treated patients.

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388

CLINICAL 1 YEAR EXPERIENCE WITH A NOVEL MULTIPOLAR IRRIGATED

ABLATION CATHETER IN AF ABLATION PROCEDURES R. Wakili, J. Siebermair, S. Fichtner, S. Sattler, M.F. Sinner, E. Klocker, S. Kaab,

H.L. Estner

Department of Medicine I, Grosshadern Clinic, University of Munich, Munich, Germany

Introduction: Pulmonary vein isolation (PVI) is an established method to treat atrial fibrillation

(AF). However, PVI is still a time consuming procedure. Thus, new methods are necessary to

improve procedural parameters, e.g. shortening of procedure time (PT). A novel multipolar

irrigated radiofrequency (RF) ablation catheter (nMARQ™) is a new tool trying to improve PVI

procedures. In this study we investigated the influence on procedural parameters using a multipolar

irrigated ablation catheter (MIAC).

Methods: 48 consecutive patients with paroxysmal AF were investigated undergoing PVI divided

into 2 groups: 1.) n=24, standard ablation catheter (SAC, Thermocool Biosense Webster©), 2.)

n=24, MIAC (nMARQ™ Biosense Webster©). Study endpoints included procedure time (PT),

fluoroscopy time (FT), number of energy applications (EA) and clinical outcome (freedom from

AF). All MIAC patients underwent phrenic nerve stimulation and esophagus temperature

monitoring during PVI as well as endoscopy post PVI for safety assessment.

Results: Patient characteristics did not differ significantly between both groups. PE was reached

in all patients in the SAC group. However, in the MIAC group complete PVI failed in 5/24 patients.

Mean FT and LA PT were similar. However, number of EA (20±1 vs. 29±4, p<0.05) and

cumulative RF time (16±1 vs. 24±5 min, p<0.001) to achieve PVI were significantly lower in

MIAC group vs. SAC. Analysis of clinical outcome revealed no differences a mean follow-up

(FU) of 263±131 days between both groups (MIAC: 85% vs. SAC: 76%). Regarding safety one

catheter charring event, one thermal esophageal lesions and one phrenic nerve palsy, despite

prophylactic stimulation, was observed in the MIAC group.

Conclusion: In our small cohort ablation with MIAC seems to still bear a potential for

complications along with important device related limitations to successfully assess and achieve

PV disconnection. Furthermore, ablation with MIAC failed to show significant benefits regarding

relevant procedural parameters or clinical outcome compared to a SAC cohort.

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389

IMPACT OF REDUCED ABLATION TIME ON CLINICAL OUTCOMES IN PAF

PATIENTS USING ARCTIC FRONT ADVANCE CRYOBALLOON (AFACA)

S. Banga1, N. Chalfoun2, A. Gauri2, D. Elmouchi2, M. Dahu2, A.T. Davis2, B. Finta2

1. University of Illinois College of Medicine at Peoria, Peoria, IL, USA

2. Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, MI, USA

Background: Cryoablation of paroxysmal atrial fibrillation (PAF) with the AFACA has technical

advantages over the older system but its use has been associated with complications.

Objective: We proposed to study the impact of shortening ablation time on the outcomes of the

AF ablation using AFACA.

Methods: We retrospectively studied 118 consecutive patients with PAF who underwent AFACA

between 7/12 – 5/13. In the conventional group (83 pts; 7/12 – 2/13) we aimed for ablation time

of 4-min/lesion and in the modified group (35 pts; 3/13-6/13), we aimed for 3 min/lesion. Ablation

times and complications including selected indicators of ‘collateral damage’ (pericarditis,

esophageal injury or fistula, transient phrenic nerve paralysis) with 3 and 6-month procedure

success were compared.

Results: In the modified time group, the total ablation time and time/lesion were reduced by 24%

(p<0.001) and 26% respectively (p < 0.001). ‘Collateral damage’ was reduced in the modified time

group (8.6% versus 24.1%; p =0.05), driven mostly by minor pericarditis. Only one major

complication occurred in the conventional group (atrio-esophageal fistula). [Table1].

Conclusions: Shortening of ablation time using AFACA resulted in significantly less complication

rate including reduced ‘collateral damage’ to mediastinal structures, while preserving optimal

clinical outcomes of cryoablation in patients with PAF. Table 1.

Parameters Conventional

(n=83)

Modified

(n=35)

p-value

Age(years) 60.9±11 59.2±11.3 0.45

Male, n (%) 49(59) 26(74) 0.12

Number of pulmonary veins per patient, n 4.0±0.4 4.0±0.4 >0.999

Average no. of lesions per patient, n 9.9±2.0 10.0±1.8 0.8

Average no. of lesions per vein, n 2.5±0.6 2.6±0.6 0.41

Average ablation time (min),n 37.0± 6.7 28.2± 6.8 <0.001

Average ablation time/lesion (min) 3.8± 0.3 2.8± 0.6 <0.001

Average ablation time/vein (min) 9.2±1.9 7.4±2.3 <0.001

Complication Rate, n (%) 23(27.7) 3(8.6) 0.02

Transient Ischemic attack, n (%) 3(3.6) 0(0) 0.55

‘Collateral damage’ n (%) 20(24.1) 3 (8.6) 0.05

Minor pericarditis, n (%) 12 (14.5) 1 (2.9) 0.11

Transient phrenic nerve palsy, n (%) 5 (6) 1 (2.9) 0.67

Esophageal injury, n (%) 1 (1.2) 1(2.9) 0.51

Atrio-esophageal fistula n (%) 1 (1.2) 0 (0) >0.999

Pulmonary vein stenosis 1(1.2) 0(0) >0.999

Total Follow up, n (%) 81(97.6) 35(100) >0.999

3-months success ±AAD, n (%) 61 (75.4) 25 (71.4) 0.82

3-6months true success (No AAD), n (%) 62 (76.5) 27 (77.1) 0.78

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390

MANAGEMENT OF GASTROINTESTINAL SYMPTOMS IN PATIENTS TREATED

WITH DABIGATRAN ETEXILATE (PRADAXA®) D.J. O'Dea1, S.K. Sanganalmath2, J. Schnee2, J. Whetteckey2, N. Ting2, C. Duffy2

1. Hudson Valley Cardiovascular Practice, Poughkeepsie, New York, NY, USA

2. Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, USA

Dabigatran etexilate (DE) is indicated to reduce risk of stroke and systemic embolism in patients

with nonvalvular atrial fibrillation (NVAF). Increased incidences of gastrointestinal symptoms

(GIS) such as abdominal discomfort were seen in trials comparing DE to warfarin.

An exploratory study evaluated 2 strategies for GIS management with DE.DE-naïve NVAF

patients with no GIS for > 2weeks were followed for 3 months taking DE. Patients reporting GIS

were randomized (1:1) to either a strategy of taking DE within 30 min after a meal or added

pantoprazole (40 mg daily). Patients whose GIS did not completely resolve with the initial strategy

were to be assigned the other as add-on therapy. Management periods lasted 4 weeks. 1067 patients

were enrolled and treated with DE. 117 patients (11%) self-reported GIS and were randomized:

58 to pantoprazole and 59 to DE + meal. In the pantoprazole group, 39 patients (67%) had complete

symptom resolution, 11 (19%) partial resolution, and 8 (14%) no resolution. In the DE + meal

group, 33 (56%) had complete resolution, 7 (12%) partial resolution, and 19 (32%) no resolution.

A descriptive P value comparing strategies was <0.05 favoring pantoprazole. For the second (add-

on) phase, 11 of 19 patients with partial or no GIS resolution taking pantoprazole added DE +

meal: 2 had symptom resolution, 6 partial resolution, and 3 no resolution or withdrew consent.

Alternatively, 14 out of 26 patients with partial or no response taking DE + meal added

pantoprazole: 6 had symptom resolution, 6 partial resolution, and 2 no resolution.

Patients who developed GIS on DE had partial or complete resolution of symptoms more

frequently on an initial management strategy that included pantoprazole. Overall, 90/117 (77%) of

patients with GIS randomized experienced complete or partial resolution of symptoms when taking

DE with a meal or concomitant pantoprazole.

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391

USEFULNESS OF DABIGATRAN IN JAPANESE PATIENTS WITH NON VALVULAR

ATRIAL FIBRILLATION T. Ariyama1, S. Iwamoto1, T. Ishii1, T. Tomaru2

1. Toho University, Funabashi, Chiba, Japan

2. Toho University Medical Center Sakura Hospital, Sakura, Chiba, Japan

Background: Recently, several novel anticoagulants have been approved for the prevention of

thromboembolic strokes as an alternative to warfarin in patients with non-valvular atrial fibrillation

(AF). However, anticoagulant effects and bleeding risks of a direct thrombin inhibitor dabigatran

have not been fully elucidated in Japan.

We studied adverse events in the dabigatran-treated group, and analyzed for risk factors of

hemorrhagic adverse events.

Methods: We retrospectively examined patients taking dabigatran or warfarin with AF in Toho

University Medical Center Sakura hospital. Anticoagulant effects were evaluated using

Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT). CHADS2 score and

HAS-BLED score were used for risk evaluation.

Results: Dabigatran was administered as anticoagulant in 70 patients and warfarin was

administered in 230 patients. Thromboembolism was observed in 15 patients with warfarin, but

was not observed with dabigatran. Bleeding complications were observed in 9 patients (12.9%)

with dabigatran and 119 (51.7%) with warfarin. In patients with dabigatran, intracranial

hemorrhage was not observed. APTT of bleeding group was 38.9±8.7 sec at trough, APTT of non-

bleeding group was 38.6±6.1 sec (p=0.96).APTT of bleeding group was 53.48.3 sec at peak, APTT

of non-bleeding group was 50.0±9.7 sec (p=0.25). PT of bleeding group was 12.6±1.3 sec, PT of

non-bleeding group was 12.1±1.8 sec (p=0.13). PT and APTT were not correlated with creatinine

level.CHADS2 score or HAS-BLED score was not correlated with bleeding. Gastric

manifestations were observed in 19 patients (27.1%) with dabigatran.

Conclusions: Dabigatran may be a safe and effective drug for the patients with AF including the

aged patients, and its anticoagulant effect is stable. However, minor bleeding may occur without

marked prolongation of APTT.

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MISCELLANEOUS

392

EVALUATING EJECTION FRACTION AND OBESITY IN A HEART FAILURE

PROGRAM PREDOMINANTLY COMPOSED OF A BLACK AND HISPANIC

POPULATION H.S. Lee, G. Pekler, B. Nunez .S. Mushiyev, F. Visco

Metropolitan Hospital, New York Medical College, New York, NY, USA

Objective: To relate the obesity paradox to ejection fraction and obesity.

Background: The obesity paradox remains controversial in the literatures. Obesity has detrimental

effects on heart failure, but has been found to be paradoxically associated with improved survival.

Method: This is a cross-sectional study. We analyzed 732 patients who were enrolled in our heart

failure program and excluded those who did not follow up or patients discharged from the

cardiology clinic. 344 patients who have been followed since 2013 were included. Using

ACC/AHA guidelines, heart failure is classified as a reduced ejection fraction (HFrEF, EF <40),

preserved ejection fraction (HFpEF, EF>50) and heart failure with an improved ejection fraction

(HFpEF(i),EF> =40). BMI (Body Mass Index) was classified according to NCEP-ATP III. All

variables were analyzed by SAS Ver. 9.4.

Results: The number of normal weight (BMI <25kg/m2), overweight (30 kg/m2>BMI >

=25kg/m2) and obesity (BMI > =30kg/m2) were 125(35.7%),121(35.1%) and 98(29.1%)

respectively. The number of patients in our selected populations of HFrEF, HFpEF and HFpEF(i)

were 228(67.9%),68(20.2%) and 40(11.9%) respectively. A preserved EF had a significant P-

value associated with the overweight group compared to our normal weight group. In addition, the

absence of diabetes mellitus, an ICD, no prior cardiac catheterization and age over 65 were

associated with a preserved EF.

Conclusion: The obesity paradox applied to our study group. The overweight group had a higher

percentage of patients with a preserved ejection fraction compared to the normal weight group.

Factors favoring a preserved EF were different among our three BMI groups. Targeted

management of related factors in heart failure could lead to different approaches in the future

treatment of heart failure.

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Abstracts - Cardiology Online · Ran Kornowski, Israel Smadar Kort, USA Santhosh K.G Koshy, USA...

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Transcript of Abstracts - Cardiology Online · Ran Kornowski, Israel Smadar Kort, USA Santhosh K.G Koshy, USA...